סרטן ריאות

מאמרים בתחום סרטן הריאות

1. Target Oncol. 2015 Jun;10(2):255-65. doi: 10.1007/s11523-014-0336-7. Epub 2014

Sep 9.

Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based

chemotherapy plus cetuximab as first-line treatment for non-small cell lung

cancer: randomized non-comparative phase IIIb NEXT trial.

Heigener DF(1), Pereira JR, Felip E, Mazal J, Manzyuk L, Tan EH, Merimsky O,

Sarholz B, Esser R, Gatzemeier U.

Author information:

(1)LungenClinic Grosshansdorf, Woehrendamm 80, 22927, Grosshansdorf, Germany,

d.heigener@lungenclinic.de.

The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of

cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly

improved survival in the first-line treatment of advanced non-small cell lung

cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755)

investigated the efficacy and safety of weekly and every 2 weeks cetuximab

maintenance therapy in this setting. Patients were treated with platinum-based

chemotherapy plus cetuximab, and those progression-free after four to six cycles

were randomized to every 2 weeks (500 mg/m(2)) or weekly (250 mg/m(2)) cetuximab

maintenance. Randomization was stratified for tumor histology and response

status. The primary endpoint for a regimen would be reached if the lower boundary

of the 95 % confidence interval (CI) for the 1-year survival rate exceeded 55 %.

A planned 480 patients were to be randomized. However, enrollment was curtailed

following a negative opinion from the European Medicines Agency with regard to

the use of cetuximab in this setting. After combination therapy, 311/583 (53.3 %)

patients without progression were randomized to maintenance therapy: 157 to every

2 weeks cetuximab and 154 to weekly cetuximab. Baseline characteristics were

balanced between these groups and exposure to cetuximab was similar. The 1-year

survival rate was 62.8 % (95 % CI, 54.7-70.0) for every 2 weeks cetuximab and

64.4 % (95 % CI, 56.2-71.4) for weekly cetuximab. Safety profiles were similar,

manageable, and in line with expectations. Therefore, in patients with advanced

NSCLC who were progression-free after four to six cycles of first-line

chemotherapy plus cetuximab, weekly and every 2 weeks cetuximab maintenance

therapy were associated with similar survival outcomes.

PMID: 25195590 [PubMed - in process]

2. Am J Clin Oncol. 2014 Jul 17. [Epub ahead of print]

Single-institution Experience of SBRT for Lung Metastases in Sarcoma Patients.

Soyfer V(1), Corn BW, Shtraus N, Honig N, Meir Y, Kollender J, Merimsky O.

Author information:

(1)Tel Aviv Medical Center, Tel Aviv University, Tel Aviv, Israel.

OBJECTIVES:: Lung metastasectomy is regarded as the standard procedure for

improving the prognosis of patients with metastatic sarcoma. Few reports are

available in the literature describing the value of stereotactic body radiation

therapy (SBRT) of lung metastases from primary sarcoma as an alternative to

surgical treatment. We therefore sought to expand the evidence base for this

modality.

MATERIALS AND METHODS:: Twenty-two patients with metastatic sarcoma to lung were

treated by SBRT. The retrospective analysis of overall survival, toxicity, and

local control of 53 treated lesions is presented in the study. Lung lesions were

grouped into 2 categories for follow-up: <10 mm or ≥10 mm diameter.

RESULTS:: Of 34 lesions <10 mm, 24 achieved complete response, 3 partial

response, and 7 stable disease. The results of 18 lesions measuring >10 mm were

as follows: 5 complete response, 5 progressive disease, and 8 stable disease. No

progressive disease of all SBRT treated lesions was found at a median follow-up

of 95 months (SD 32). Five-year overall survival of the entire group was 62% from

the time of diagnosis and 50% from start of treatment. The treatment was well

tolerated with minimal, mainly skin toxicity.

CONCLUSION:: SBRT is an effective tool that might be used as an alternative to

operative treatment of lung metastases in sarcoma patients.

PMID: 25036473 [PubMed - as supplied by publisher]

3. Lung. 2014 Oct;192(5):759-63. doi: 10.1007/s00408-014-9604-7. Epub 2014 Jun 26.

EGFR mutation testing practice in advanced non-small cell lung cancer.

Bar J(1), Cyjon A, Flex D, Sorotsky H, Biran H, Dudnik J, Peylan-Ramu N, Peled N,

Nechushtan H, Gips M, Katsnelson R, Rosenberg SK, Merimsky O, Onn A, Gottfried M.

Author information:

(1)Department of Oncology, Institute of Oncology, Sheba Medical Center, Tel

Hashomer, 52621, Ramat Gan, Israel, bar.jair@gmail.com.

PURPOSE: Testing tumor samples for the presence of a mutation in the epithelial

growth factor receptor (EGFR) gene is recommended for advanced non-squamous

non-small cell lung cancer (NSCLC) patients. We aimed to collect data about

common practice among Medical Oncologists treating lung cancer patients,

regarding EGFR mutation testing in advanced NSCLC patients.

METHODS: An internet-based survey was conducted among members of the Israeli

Society for Clinical Oncology and Radiotherapy involved in the treatment of lung

cancer patients.

RESULTS: 24 Oncologists participated in the survey. The participants encompass

the Oncologists treating most of the lung cancer patients in Israel. 79% of them

use EGFR testing routinely for all advanced NSCLC patients. Opinions were split

regarding the preferable biopsy site for EGFR testing material. 60% of

participants recommend waiting for EGFR test results prior to initiation of

first-line therapy.

CONCLUSIONS: EGFR testing is requested in Israel routinely by most treating

Oncologists for all advanced NSCLC patients, regardless of histology. In most

cases, systemic treatment is deferred until the results of this test are

received.

PMID: 24964874 [PubMed - indexed for MEDLINE]

4. Lancet Oncol. 2014 Jan;15(1):59-68. doi: 10.1016/S1470-2045(13)70510-2. Epub 2013

Dec 9.

Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III

non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial.

Butts C(1), Socinski MA(2), Mitchell PL(3), Thatcher N(4), Havel L(5), Krzakowski

M(6), Nawrocki S(7), Ciuleanu TE(8), Bosquée L(9), Trigo JM(10), Spira A(11),

Tremblay L(12), Nyman J(13), Ramlau R(14), Wickart-Johansson G(15), Ellis P(16),

Gladkov O(17), Pereira JR(18), Eberhardt WE(19), Helwig C(20), Schröder A(20),

Shepherd FA(21); START trial team.

Collaborators: Shepherd F, Butts C, Thatcher N, Socinski M, Mitchell P, Talbot D,

Gillen D, Whang-Peng J, Thirwell M, Seeber S, Braun D, Schröder A, Falk M,

Günther B, Marschner JP, Helwig C, Loos A, Tyroller K, Schüler A, Ferrande L,

Gaumond B, Olchowka K, Koh P, Mackiewicz M, Sylvester E, Wallis N, Joerg I,

Schick R, Munn J, Best M, Campbell A, Laszczewska V, Parvez T, Ferro A, Tremblay

L, Sadjadian P, Smit E, Park K, Kotz K, Borghaei H, Stehle I, Ismael C, Alam Z,

Engel-Riedel W, Stigt J, García Girón C, Kumar K, Oton A, Jäger E, Pasccon GV,

von Ksienski D, Pawel J, van den Borne B, Trigo JM, Lester E, Nader D, Kortsik C,

Martin C, Murray N, Serke M, van den Heuvel M, Vazquez S, March R, Li Z, Wolf M,

Pallotta M, MacNeil M, Georgoulias V, van Ojik H, López Vivanco G, Masri M,

Espinoza A, Rüttinger D, Perazzo F, Hirsh V, Kosmidis P, Krouwels F, Paredes A,

Shinn L Jr, Limentani S, Eschbach C, Ponce W, Findlay B, Pectasides D,

Chmielowska E, Viñolas N, Mirtsching B, Pincus S, Gahn B, Fein L, Burkes R,

Syrigos K, Jagiello-Gruszfeld A, Massuti B, Okazaki I, Young D, Kollmeier J,

Zarbá J, MacCormick R, Fountzilas G, Kozielski J, Gonzalez-Larriba JL, Saleh M,

Nugent F 3rd, Gütz S, Bella S, Wang J, Samantas E, Krzakowski M, Barragán PL,

Curran C, Chaudhry A, Wilke H, Bagnes C, Sun Y, Lee V, Lesniewski-Kmak K, Alonso

G, Gabrail N, Ndum P, Reck M, Mitchell P, Koubková L, Mok T, Ramlau R, Bosch J,

Abbott K, Beall C, Shepherd F, Millward M, Reiterer P, Albert I, Rysz-Postawa B,

Moreno MA, Bellam S, Nieva J, Maksymiuk A, Boyer M, Roubec J, Losonczy G, Labij

V, de Castro J, Charu V, Modi S, Butts C, McCaffrey E, Salajka F, Szima B,

Rusinowska Z, Wichardt-Johansson G, Erlich R, Dudek A, Ellis P, Pavlakis N, Havel

L, Zsiray M, Szczesna A, Ewers SV, Page R, Ghazal H, Lee C, Crombie C, Zemanová

M, Szabó P, Freier B, Henriksson R, Rao H, Gitlitz B, Desjardins P, Kirsten F,

Hansen O, Bittner N, Kus J, Nyman J, Sanborn R, Harrer G, Vergidis D, Pirker R,

Ryberg M, Bittner N, Sawrycki P, Nilsson K, Bruno D, Mehdi A, Cohen V, Kolb R,

Louridi JB, Chacko R, Chojnacka M, Bergström S, Shah S, Jones C, Bebb G,

Mohn-Staudner A, Robinet G, Raja R, Nawrocki S, Zippelius A, Shirinian M,

Gotovkin E, Soulières D, Greil R, Zalcman G, Julka PK, Fijuth J, Pless M, Abdel

Karim I, Soo R, Thropay J, Hilbe W, Choma D, Digumarti R, Barata FJ, Mach N,

Neerukonda L, Kasan P, Akunyili I, Kropfmüller R, Verkindre C, Advani S, Teixeira

E, Yang CH, Bonomi P, Packan T, Argiris A, Samonigg H, Dumont P, Vamsy M,

Almodovar MT, Liu MC, Rakkar A, Berzinec P, Edelman M, Vansteenkiste J, Tourani

JM, O'Byrne K, Araújo A, Hsia TC, Rao R, Kang JH, Natale R, Lambrechts M, Gervais

R, Cyjon A, Dediu M, Chang GC, Dowlati A, Kim SW, Ottensmeier C, Humblet Y,

Schott R, Dudnik J, Anghel R, Chen YM, Weiss J, Lee JS, Collinson M, Duplaquet F,

Spaeth D, Gottfried M, Ciuleanu TD, Tsao CH, Spira A, Kim JH, Thomas G, Louis R,

Barlesi F, Merimsky O, Volovat C, Kuo HP, Langer C, Heo DS, O'Brien M, Clinckart

F, Fabre-Guillevin E, Peylan-Ramu N, Ganea Motan DE, Huang MS, Vrindavanam N,

Gebbia V, MacGregor C, Verhoeven D, Pibarot M, Sulkes A, Patran M, Su WC, Bhanja

U, Ciardiello F, Tjulandin S, de Azevedo S, Westeel V, Wollner M, Sirbu D, Lin

MC, Hoffman S, Grossi F, Popov V, Barrios CH, Mornex F, Onn A, Cheporov S, Price

A, Bednar M, Aglietta M, Goldberg V, Delgado G, Thomas M, Platania M, Gladkov O,

Snee M, Bhaskar B, Contu A, Medvedev V, Franke FA, Waller C, Siena C, Mikhaylov

S, Dorey N, Caputto S, Gridelli C, Khasanov R, Malzyner A, Eberhardt W, Amadori

D, Lubennikov V, Marshall E, Chen LC, Guevara Torres A, Santoro A, Nugué P,

Schneller F, De Marinis F, Akhmadullina L, Ezhil M, West H, Trigueros Velázquez

M, Scagliotti G, Pizão, Griesinger F, Longo L, Byakhov M, Hicks J, Berg A,

Ramírez Márquez M, Tiseo M, Segalla, Hildebrandt G, Martoni A, Moiseyenko V,

Taylor P, Hays J, Arrieta Rodriguez OG, Caffo O, Mathias CM, Huber R, Witt C,

Murad A, Höffken G, Gorini C, Zukin M, Iacobelli S, Pereira J, Schreiber J,

Wehler T.

Comment in

Lancet Oncol. 2014 Jan;15(1):5-6.

BACKGROUND: Effective maintenance therapies after chemoradiotherapy for lung

cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific

cancer immunotherapy tecemotide improves survival in patients with stage III

unresectable non-small-cell lung cancer when given as maintenance therapy after

chemoradiation.

METHODS: The phase 3 START trial was an international, randomised, double-blind

trial that recruited patients with unresectable stage III non-small-cell lung

cancer who had completed chemoradiotherapy within the 4-12 week window before

randomisation and received confirmation of stable disease or objective response.

Patients were stratified by stage (IIIA vs IIIB), response to chemoradiotherapy

(stable disease vs objective response), delivery of chemoradiotherapy (concurrent

vs sequential), and region using block randomisation, and were randomly assigned

(2:1, double-blind) by a central interactive voice randomisation system to either

tecemotide or placebo. Injections of tecemotide (806 μg lipopeptide) or placebo

were given every week for 8 weeks, and then every 6 weeks until disease

progression or withdrawal. Cyclophosphamide 300 mg/m(2) (before tecemotide) or

saline (before placebo) was given once before the first study drug

administration. The primary endpoint was overall survival in a modified

intention-to-treat population. This study is registered with ClinicalTrials.gov,

number NCT00409188.

FINDINGS: From Feb 22, 2007, to Nov 15, 2011, 1513 patients were randomly

assigned (1006 to tecemotide and 507 to placebo). 274 patients were excluded from

the primary analysis population as a result of a clinical hold, resulting in

analysis of 829 patients in the tecemotide group and 410 in the placebo group in

the modified intention-to-treat population. Median overall survival was 25.6

months (95% CI 22.5-29.2) with tecemotide versus 22.3 months (19.6-25.5) with

placebo (adjusted HR 0.88, 0.75-1.03; p=0.123). In the patients who received

previous concurrent chemoradiotherapy, median overall survival for the 538 (65%)

of 829 patients assigned to tecemotide was 30.8 months (95% CI 25.6-36.8)

compared with 20.6 months (17.4-23.9) for the 268 (65%) of 410 patients assigned

to placebo (adjusted HR 0.78, 0.64-0.95; p=0.016). In patients who received

previous sequential chemoradiotherapy, overall survival did not differ between

the 291 (35%) patients in the tecemotide group and the 142 (35%) patients in the

placebo group (19.4 months [95% CI 17.6-23.1] vs 24.6 months [18.8-33.0],

respectively; adjusted HR 1.12, 0.87-1.44; p=0.38). Grade 3-4 adverse events seen

with a greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024

patients in the tecemotide group vs 21 [4%] of 477 patients in the placebo

group), metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia

(23 [2%] vs 12 [3%]). Serious adverse events with a greater than 2% frequency

with tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the

placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous

system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ

between groups.

INTERPRETATION: We found no significant difference in overall survival with the

administration of tecemotide after chemoradiotherapy compared with placebo for

all patients with unresectable stage III non-small-cell lung cancer. However,

tecemotide might have a role for patients who initially receive concurrent

chemoradiotherapy, and further study in this population is warranted.

FUNDING: Merck KGaA (Darmstadt, Germany).

PMID: 24331154 [PubMed - indexed for MEDLINE]

5. Br J Radiol. 2013 Aug;86(1028):20130258. doi: 10.1259/bjr.20130258. Epub 2013 May

24.

Hypofractionated adjuvant radiation therapy of soft-tissue sarcoma achieves

excellent results in elderly patients.

Soyfer V(1), Corn BW, Kollender Y, Issakov J, Dadia S, Flusser G, Bickels J,

Meller I, Merimsky O.

Author information:

(1)Department of Oncology, Tel Aviv Sourasky Medical Center, Ashdod, Israel.

OBJECTIVE: Adjuvant radiation therapy (RT) is an essential part of combined

limb-sparing treatment of soft-tissue sarcoma (STS). Elderly or medically unfit

patients often have difficulty in completing 6-7 weeks of standard fractionated

daily treatment. Our aim was to evaluate the efficacy of a hypofractionated

adjuvant approach with RT for STS in elderly and debilitated patients.

METHODS: 21 elderly patients were treated with a short course of adjuvant RT

(39-48 Gy, 3 Gy per fraction) for STS. The medical records of the patients were

retrospectively reviewed for local or distant recurrence and side effects of RT.

RESULTS: At a mean 26 months of follow-up, three local recurrences (14%) were

detected. Eight patients (38%) had lung metastases during the observed period.

Three of them died from metastatic disease. The hypofractionated radiation was

well tolerated with minimum long-term side effects.

CONCLUSION: Hypofractionated adjuvant radiation appears to be an effective

treatment in terms of local control in elderly and debilitated patients.

ADVANCES IN KNOWLEDGE: The results of this study might provide an alternative to

commonly used standard fractionation of radiotherapy in sarcoma patients.

PMCID: PMC3745062

PMID: 23709514 [PubMed - indexed for MEDLINE]

6. Oncol Lett. 2013 Feb;5(2):424-426. Epub 2012 Dec 5.

The evolution in melanoma treatment as a reflection of precision-oriented

medicine.

Kushnir I(1), Merimsky O.

Author information:

(1)Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239,

Israel.

Until recently, metastatic melanoma was a disease with limited treatment options

and a poor prognosis. Dacarbazine was accepted as the standard treatment for

melanoma in the 1970s, and despite inducing an overall survival of approximately

7.4 months, it remained so until relatively recently. In the last few years,

significant advances in the molecular understanding of this disease have

facilitated the development of novel and promising drugs. Precision-oriented

medicine is currently revolutionizing the practice of oncology. Targeted

therapies have demonstrated great potential in treating melanoma and various

other types of cancer, including breast, colorectal and non-small cell lung

cancer. Here, we review the evolution of melanoma treatment from single-agent

chemotherapy to combination therapy, the emergence of immunotherapy in melanoma

and the development of targeted therapies, such as the use of the BRAF inhibitor

as a treatment agent. The ability to treat melanoma according to the fingerprint

of the tumor reflects an overall change in the practice of oncology.

PMCID: PMC3573132

PMID: 23420786 [PubMed]

7. Ann Oncol. 2012 Oct;23 Suppl 7:vii92-9.

Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for

diagnosis, treatment and follow-up.

ESMO / European Sarcoma Network Working Group.

Collaborators: Blay JY, Blomqvist C, Bonvalot S, Boukovinas I, Casali PG, De

Alava E, Dei Tos AP, Dirksen U, Duffaud F, Eriksson M, Fedenko A, Ferrari A,

Ferrari S, del Muro XG, Gelderblom H, Grimer R, Gronchi A, Hall KS, Hassan B,

Hogendoorn P, Hohenberger P, Issels R, Joensuu H, Jost L, Jurgens H, Kager L, Le

Cesne A, Leyvraz S, Martin J, Merimsky O, Nishida T, Picci P, Reichardt P,

Rutkowski P, Schlemmer M, Sleijfer S, Stacchiotti S, Taminiau A, Wardelmann E.

PMID: 22997462 [PubMed - indexed for MEDLINE]

8. Oncol Rep. 2012 Aug;28(2):721-7. doi: 10.3892/or.2012.1824. Epub 2012 May 18.

Efficacy and safety of first-line erlotinib in elderly patients with advanced

non-small cell lung cancer.

Merimsky O(1), Cheng CK, Au JS, von Pawel J, Reck M.

Author information:

(1)Division of Oncology, Tel Aviv Medical Center, Tel-Aviv 64239, Israel.

oferm@tasmc.health.gov.il

TaRceva LUng cancer Survival Treatment (TRUST) was an open-label, phase IV study

of advanced non-small cell lung cancer (NSCLC). Patients failing or unsuitable

for chemotherapy or radiotherapy received erlotinib 150 mg/day until progression.

We examined a subpopulation of elderly patients (≥70 years) receiving first-line

erlotinib (n=485) in TRUST. In this subpopulation, disease control rate (n=356

with best response data available) was 79% (vs. 69% for the overall TRUST

population; p<0.0001); median progression-free survival (PFS) was 4.57 months

[95% confidence interval (CI), 3.68-5.22]; median overall survival (OS) was 7.29

months (95% CI, 6.27-8.67); and one-year survival, was 36.6%. PFS and OS were

significantly longer in patients developing rash, compared to those without, and

in those with good performance status (PS; 0/1), compared to poor PS (≥2).

Eighty-seven subpopulation patients (18%) had an erlotinib-related AE; other than

the protocol-defined frequent adverse events (AEs); 4% had a grade ≥3

erlotinib-related AE, 7% had an erlotinib-related serious AE. In the

subpopulation, dose reductions were required in 27%, most (97%) were reductions

to 100 mg/day; treatment was discontinued in 10%, and one death was associated

with treatment-related toxicity (<1%). Erlotinib was effective and well-tolerated

and may be considered for elderly patients with advanced NSCLC who are unsuitable

for standard first-line chemotherapy or radiotherapy.

PMID: 22614912 [PubMed - indexed for MEDLINE]

9. Cancer Lett. 2011 Nov 28;310(2):207-15. doi: 10.1016/j.canlet.2011.07.002. Epub

2011 Jul 14.

Combining an EGFR directed tyrosine kinase inhibitor with autophagy-inducing

drugs: a beneficial strategy to combat non-small cell lung cancer.

Gorzalczany Y(1), Gilad Y, Amihai D, Hammel I, Sagi-Eisenberg R, Merimsky O.

Author information:

(1)Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel

Aviv University, Tel Aviv 69978, Israel.

The potential therapeutic value of combinatorial regimens based on an EGF

receptor tyrosine kinase inhibitor (TKI) and autophagy inducing drugs was

evaluated by comparing their molecular impacts on H1299 and A549 non-small cell

lung cancer (NSCLC) cells, which overexpress wild type EGF receptor, but are

either deficient or have wild type p53 alleles, respectively. We show that H1299

cells display a considerably lower sensitivity to erlotinib treatment, which can

be restored by combining erlotinib with rapamycin or with imatinib, though to a

lesser extent. Cytotoxicity was associated with increased autophagy and

hyperpolarization of the mitochondrial membrane potential. Therefore, combining

an EGF receptor directed TKI with an autophagy-inducing drug, preferably,

rapamycin, might be beneficial in treating poor responding NSCLC patients.

PMID: 21807458 [PubMed - indexed for MEDLINE]

10. J Thorac Oncol. 2008 Sep;3(9):994-1002. doi: 10.1097/JTO.0b013e31818396cb.

Oral vinorelbine and cisplatin as induction chemotherapy and concomitant

chemo-radiotherapy in stage III non-small cell lung cancer: final results of an

international phase II trial.

Krzakowski M(1), Provencio M, Utracka-Hutka B, Villa E, Codes M, Kuten A, Henke

M, Lopez M, Bell D, Biti G, Merimsky O, Beorchia A, Riggi M, Caux NR, Pouget JC,

Dubray B, David P.

Author information:

(1)Institut de Recherche Pierre Fabre, Boulogne Billancourt, France.

INTRODUCTION: Cisplatin in combination with vinorelbine has reported an optimal

activity/tolerance ratio when used in combination with radiotherapy in locally

advanced unresectable non-small cell lung cancer. The currently available oral

formulation of vinorelbine should be easier to use assuming a similar activity

profile. An international phase II trial with vinorelbine oral and cisplatin as

induction followed by oral vinorelbine and cisplatin with concomitant

radiotherapy was implemented to evaluate the efficacy in terms of objective

response (OR) following this combination as primary end point and duration or

response, progression-free survival, overall survival, and safety as secondary

endpoints.

MATERIAL AND METHODS: The study included patients between 18 and 75 years, with

histologically proven untreated locally advanced inoperable stage IIIA/IIIB

(supraclavicular lymph nodes and pleural effusion excluded) non-small cell lung

cancer, adequate bone marrow, hepatic and renal function, Karnofsky performance

status >/=80%. Patients were treated with oral vinorelbine 60 mg/m day 1,8 cycle

1 and 80 mg/m day 1,8 cycle 2 (if no grade 3-4 toxicity) and cisplatin 80 mg/m

day 1 every 3 weeks for 2 cycles as induction. Patients without progression

received oral vinorelbine 40 mg/m day 1, 8 and cisplatin 80 mg/m day 1 every 3

weeks for 2 more cycles with radiotherapy 66 Gy in 6.5 weeks.

RESULTS: Patient and disease characteristics (n = 54) included: median age 57

years; female sex 24%; stage IIIA 48% and IIIB 52%; Squamous carcinoma 59%,

Karnofsky performance status 100% (range, 80-100%) 50%, patients >/=5% weight

loss at baseline 7%. Relative dose intensities of oral vinorelbine/cisplatin were

86%/93% and 97%/98% at induction and in combination with radiotherapy,

respectively. Forty-one patients (76%) increased oral vinorelbine from 60 to 80

mg/m day during induction (reasons for nonescalation: hematological 7 patients,

nonhematological 2 patients, error 4 patients). After two cycles of chemotherapy

induction, the OR intent-to-treat in the 54 patients was 37%. Toxicities during

induction were as follows: Neutropenia G3-4 (28%), Febrile Neutropenia (7%),

nausea G3 (11%), vomiting G3-4 (9%), anorexia G3 (4%), diarrhea G4 (2%),

constipation G3 (2%). Forty-seven out of 54 (87%) patients received concomitant

chemo-radiotherapy.Median radiotherapy delivered dose was 66 Gy. Tolerance: 9% G3

Neutropenia; 4% G3 dysphagia/radiation; 2% G3 radiation dermatitis. Late

pulmonary fibrosis was reported in one patient (1.8%). One month after completion

of chemo-radiotherapy, the overall OR intent-to-treat in the 54 patients was 54%

(95% CI: 40-67%). With a median follow-up of 37 months (95% CI: 34-41) the median

progression-free survival and overall survival were: 12.5 (95% CI: 9.6-16.4) and

23.4 (95% CI: 17.6-29.8) months, respectively.

CONCLUSION: Oral vinorelbine in combination with cisplatin is an effective

combination in stage IIIA/IIIB patients. The excellent tolerance profile allowed

to complete concomitant chemo-radiotherapy in 87% of patients. Oral vinorelbine

in combination with cisplatin is a new and promising option that facilitates the

administration of concomitant chemo-radiotherapy with high rates of treatment

completion.

PMID: 18758302 [PubMed - indexed for MEDLINE]

11. Br J Ophthalmol. 2007 Jan;91(1):74-5. Epub 2006 Aug 30.

Decreased prevalence of asymptomatic choroidal metastasis in disseminated breast

and lung cancer: argument against screening.

Barak A(1), Neudorfer M, Heilweil G, Merimsky O, Lowenstein A, Inbar M,

Yaal-Hahoshen N.

Author information:

(1)Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Sackler Faculty

of Medicine, Tel Aviv University, 6 Weizman Street, Tel Aviv 64239, Israel.

adielbarak@gmail.com

AIM: To determine the frequency of visually asymptomatic choroidal metastases in

patients with disseminated breast and lung carcinomas in order to establish

optimal patient management policies.

METHODS: All patients with confirmed metastatic disease treated in our

institution between January 2002 and December 2003 were invited to undergo a

funduscopic examination and a B-scan ultrasound evaluation.

RESULTS: Of the 169 study participants, 77 had breast cancer (64 with metastases

in one organ and 13 with multiple-organ involvement) and 92 had lung cancer (85

with metastases in one organ and 7 with multiple-organ involvement). No patient

with metastatic breast cancer and two patients with metastatic lung disease (each

with multiple-organ involvement) were found to have choroidal metastases. The

choroidal metastases were detected by both the funduscopic and ultrasound

examinations.

CONCLUSIONS: The 2.17% incidence of choroidal metastasis in disseminated lung

cancer and the 0% incidence in disseminated breast cancer speaks against the

practicality of screening for early detection of choroidal metastasis among these

patients, even though it would lead to early implementation of appropriate, often

vision saving, therapeutic management. Its low incidence probably testifies to

progress achieved by enhanced systemic oncological treatment policies that have

been introduced into routine patient management over the past few years.

PMCID: PMC1857549

PMID: 16943227 [PubMed - indexed for MEDLINE]

12. Int J Oncol. 2005 Feb;26(2):475-82.

Induction of apoptosis in non-small lung carcinoma cell line (H1299) by

combination of anti-asthma drugs with gemcitabine and cisplatin.

Merimsky O(1), Hirsh L, Dantes A, Land-Bracha A, Suh BS, Amsterdam A.

Author information:

(1)Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel Aviv Sourasky

Medical Center, Tel Aviv University, Tel Aviv, Israel. oferm@tasmc.health.gov.il

Gemcitabine and cisplatin are commonly used in chemotherapy, however, these drugs

may cause severe cytotoxic side effects. Theophylline and aminophylline are

commonly used as anti-asthma drugs and can block anti-phosphodiesterase activity.

We examined whether these methylxanthins could effect lung cancer cell survival

and synergise with gemcitabine and cisplatin to induce apoptosis. We found that

theophylline induced apoptosis in the cultured H1299 cell line already at

concentrations of 30 microg/ml, reaching an ED50% at 100 microg/ml. In contrast,

aminophylline induced apoptosis at concentrations of 300 microg/ml and 17%

apoptosis was evident at concentrations as high as 900 microg/ml, which is a

lethal dose for in vivo treatment. Cisplatin induced apoptosis with ED50% of 0.8

microg/ml, while gemcitabine induced apoptosis with ED50% of 20 ng/ml. Using a

combination of 20 microg/ml of theophylline (calculated as an effective but not

toxic anti-asthma drug) with 10 ng/ml gemcitabine or with 0.3 microg/ml cisplatin

significantly elevated incidence of apoptosis compared to gemcitabine or

cisplatin alone at similar concentrations. In contrast, an observed synergistic

effect between aminophylline and gemcitabine was evident only at concentrations

of 80 microg/ml and 10 ng/ml respectively. However, no effect was apparent in

combination doses of aminophylline (80 microg/ml) with cisplatin (0.3 microg/ml).

The combined treatments involved reduction in the intracellular level of the

anti-apoptotic Bcl-2 gene product. This corresponded with the extent of apoptosis

induced by the various drug combinations. Thus, theophylline is significantly

more effective than aminophylline in increasing the sensitivity of the H1299 lung

cancer cells to the induction of cell death by gemcitabine and cisplatin. Thus,

combination of theophylline with these drugs may permit a reduction in the

effective dose needed in chemotherapy treatment of lung cancer patients.

PMID: 15645133 [PubMed - indexed for MEDLINE]

13. Biochem Pharmacol. 2004 Sep 15;68(6):981-8.

Phosphodiesterase inhibitors as anti-cancer drugs.

Hirsh L(1), Dantes A, Suh BS, Yoshida Y, Hosokawa K, Tajima K, Kotsuji F,

Merimsky O, Amsterdam A.

Author information:

(1)Department of Molecular Cell Biology, The Weizmann Institute of Science,

Rehovot 76100, Israel.

It is well known that high intracellular levels of cAMP can effectively kill

cancer cells in vitro. Unfortunately substances elevating cAMP such as forskolin,

8-bromo-cAMP, 8-chloro-cAMP, monobutiryl or dibutiryl cAMP are not recommended to

be used as anti-cancer drugs because of their high cytotoxicity. In contrast

blockers of phosphodieterases such as theophylline and aminophylline, which could

elevate intracellular cAMP, are commonly used as anti-asthma drugs reaching

concentrations in the blood of 10-20 microg/ml. We tested the effectiveness of

theophylline and aminophylline to induce cell death alone or in combination with

common anti-cancer drugs such as cisplatin and gemcitabine (gemzar). We examined

such drug combinations in the induction of cell death in a variety of carcinoma

cell lines derived from human ovarian, prostate and lung cancer and in granulosa

cell line transformed by SV40 and Ras oncogene. While theophylline could induce

moderate cell death alone, at 20-25 microg/ml concentrations, aminophylline was

ineffective at this concentration. Theophylline (at 15-25 ng/ml) was found in all

four representative cell lines to synergize with gemcitabine or cisplatin to

induce programmed cell death, which permits a reduction in the effective doses of

cisplatin and gemcitabine by 2-3-fold. The effect of theophylline in induction of

apoptosis involved reduction of intracellular levels of Bcl2. Such a reduction

was proportional to the extent of apoptosis induced by theophylline as well as by

the combined drug treatments. Therefore, we propose that theophylline should be

considered as a potential anti-cancer drug in combination with other

chemotherapeutic drugs. Screening of other phosphodiesterase blockers, which are

not severely toxic, could open a possibility to improved chemotherapeutic cancer

treatments with reduced undesired side-effects. A clinical trial, using

theophylline as an anti-cancer drug, is currently being conducted in lung cancer

patients.

PMID: 15313391 [PubMed - indexed for MEDLINE]

14. Ann Oncol. 2004 Apr;15(4):610-2.

Targeting pulmonary metastases of renal cell carcinoma by inhalation of

interleukin-2.

Merimsky O(1), Gez E, Weitzen R, Nehushtan H, Rubinov R, Hayat H, Peretz T,

Ben-Shahar M, Biran H, Katsenelson R, Mermershtein V, Loven D, Karminsky N,

Neumann A, Matcejevsky D, Inbar M.

Author information:

(1)Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel-Aviv Sourasky

Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv,

Israel. oferm@tasmc.health.gov.il

INTRODUCTION: Pulmonary metastases of renal cell carcinoma (RCC) are associated

with poor prognosis. Inhalation therapy with interleukin-2 (IL-2) is thus an

appealing method for palliation. This multicenter study summarizes the national

experience of IL-2 inhalation in patients with lung metastases of RCC.

PATIENTS AND METHODS: Forty patients (median, 66.5 years of age) with

radiologically documented progressing pulmonary metastases were enrolled. All

patients had to be able to comply with inhalation technique, and were not

candidates for other treatment options. Twenty-eight patients were systemic

treatment-naïve. The protocol included three daily inhalations of IL-2 to a total

dose of 18 MU. Treatment had to be continued until one of the following occurred:

progression; a complete response; a life threatening toxicity; or patient

refusal. Response was assessed using the Response Evaluation Criteria in Solid

Tumors (RECIST) system.

RESULTS: The disease-control rate reached 57.5%, with a partial response rate of

2.5% and a disease stabilization rate of 55%. Median time to progression was 8.7

months. The main side-effects were cough and weakness.

CONCLUSIONS: Inhalation of IL-2 for the treatment of pulmonary metastases in RCC

is feasible, tolerable and beneficial in controlling progressive disease for

considerable periods of time. The definition of response of biological therapy

may need to be re-assessed and modified: stable disease should be regarded as a

favorable response.

PMID: 15033668 [PubMed - indexed for MEDLINE]

15. Isr Med Assoc J. 2004 Jan;6(1):34-8.

Palliative treatment for advanced or metastatic osteosarcoma.

Merimsky O(1), Kollender Y, Inbar M, Meller I, Bickels J.

Author information:

(1)Unit of Soft Tissue and Bone Oncology, Tel Aviv Sourasky Medical Center, Tel

Aviv, Israel. oferm@tasmc.health.gov.il

PMID: 14740508 [PubMed - indexed for MEDLINE]

16. Int J Oncol. 2002 Apr;20(4):839-43.

A possible role for IVIg in the treatment of soft tissue sarcoma: a clinical case

and an experimental model.

Merimsky O(1), Meller I, Inbar M, Bar-Yehuda S, Shoenfeld Y, Fishman P.

Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239,

Israel. merimsky@zahav.net.il

A patient with a malignant peripheral nerve sheath tumor (MPNST) was treated with

IVIg for multiple sclerosis. Her MPNST course was remarkably longer and more

indolent than expected; she achieved a disease-free interval (DFI) of 30 months.

Seven other patients, who were not treated by IVIg, had a relatively aggressive

course (median DFI 3 months). These results led us to examine the effect of IVIg

on the growth of sarcoma in vitro and in vivo in an experimental model of

MCA-bearing mice. When added to MCA-105 sarcoma cell cultures, IVIg produced a

dose-dependent inhibitory effect on [(3)H]-thymidine incorporation. The maximal

inhibitory effect was at a concentration of 50 mg/ml IVIg. Cell cycle analysis

revealed a hypodiploid peak at the lower fluorescence values which appeared in

the samples treated with IVIg. These results demonstrate that the

anti-proliferative activity results from an apoptotic effect of IVIg on the tumor

cells. In a second set of experiments, we evaluated the capability of IVIg, when

administered orally or subcutaneously, to inhibit the growth of MCA-105 sarcoma

lung metastases. A decrease in the mean lung weight was observed in the mice that

were treated by s.c. or oral administration, the latter being more effective. A

possible role for IVIg in the treatment of MPNST and other soft tissue sarcomas

is suggested.

PMID: 11894134 [PubMed - indexed for MEDLINE]

17. Ann Oncol. 2001 Aug;12(8):1127-31.

Correlation between c-erbB-4 receptor expression and response to

gemcitabine-cisplatin chemotherapy in non-small-cell lung cancer.

Merimsky O(1), Staroselsky A, Inbar M, Schwartz Y, Wigler N, Mann A, Marmor S,

Greif J.

Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv University,

Israel. merimsky@zahav.net.il

BACKGROUND: While the overexpression of c-erbB gene family in several

malignancies is associated with poorer prognosis, the association between the

expression of the cellular markers and the response to chemotherapy is not yet

clear. In this study we investigated the expression of c-erbB-4 receptor in NSCLC

and correlated it with the response to gemcitabine-cisplatin combination

chemotherapy.

PATIENTS AND METHODS: Forty-three NSCLC patients with histologically or

cytologically proven disease were treated with gemcitabine-cisplatin combination

chemotherapy. Immunohistochemical stains for c-erbB-4 receptor were performed in

20 cases on paraffin sections using the avidin-biotin-peroxidase method.

RESULTS: Two patients achieved complete response (5%), and 16 achieved partial

response (37%) yielding an overall objective response rate of 42%. Minimal

response was observed in seven patients (16%) and disease stabilization in 7%.

Immunohistochemical stain was positive for the presence of c-erbB-4 receptor in

25% of patients, and negative in 75%. No response was documented in c-erbB-4

positive patients (0 of 5) while an objective response (complete, partial or

minimal) was seen in 11 of 15 (73%) c-erbB-4 negative patients. Negative stain

for c-erbB-4 significantly favored response to gemcitabine-cisplatin combination

(P < 0.01).

CONCLUSION: C-erbB-4 expression status showed no correlation with survival and

cannot be accepted at this time as a guiding factor for therapeutic management.

These interesting results deserve further evaluation in a large-scale prospective

trial before treatment recommendations on the basis of c-erbB-4 presence can be

finally made.

PMID: 11583195 [PubMed - indexed for MEDLINE]

18. Oncology. 2001;60(1):55-9.

Is forequarter amputation justified for palliation of intractable cancer

symptoms?

Merimsky O(1), Kollender Y, Inbar M, Lev-Chelouche D, Gutman M, Issakov J, Mazeh

D, Shabat S, Bickels J, Meller I.

Author information:

(1)Department of Oncology, The Tel-Aviv Sourasky Medical Center, Tel-Aviv,

Israel. merimsky@zahav.net.il

BACKGROUND: Limb-sparing surgery has replaced the radical surgical approach for

treating limb sarcomas in most cases. Amputation has been advocated as a

palliative procedure for symptomatic locally advanced disease that has already

failed to respond to radiation therapy, chemotherapy and limited surgery.

METHODS: Twelve patients with advanced malignant tumors involving the shoulder

girdle or the proximal humerus underwent forequarter amputation (FQA) for

palliative purposes. The tumor-related local problems were severe pain, limb

dysfunction, tumor fungation, bleeding (requiring emergency FQA in one case) and

infection. The preoperative Karnofsky performance status (KPS) in our series

ranged from 30 to 70%.

RESULTS: No perioperative mortality was observed. The morbidity was well

tolerated by the patients. The KPS improved in most of the patients, and was

assessed as 90-100% in 9 of the 12 patients. Overall, quality of life was

reported to be at least moderately improved by 2 out of 3 patients. Survival was

measured in months (3-24 months), but ultimately had no meaning since the

procedure was palliative. Lung metastases were the dominant cause of death in our

patients.

CONCLUSIONS: The results of FQA in our series point to its feasibility and the

gain in quality of life and performance status in severely ill patients with

advanced malignancies. Local symptoms and signs were controlled, and quality of

life was restored.

PMID: 11150909 [PubMed - indexed for MEDLINE]

19. Acta Oncol. 2000;39(4):491-3.

Correlative study of preoperative transthoracic core cutting needle biopsy of

focal thoracic lesions and thoracotomy findings.

Greif J(1), Merimsky O, Marmur S, Staroselsky AN, Schwarz Y.

Author information:

(1)Institute of Pulmonology, Tel Aviv Sourasky Medical Center, Sackler Faculty of

Medicine, Tel Aviv University, Israel.

We conducted a retrospective study to determine the clinical utility of

percutaneous core needle biopsy (PCNBx) in 36 patients with peripheral focal

chest lesions who later underwent thoracic surgery for diagnostic or therapeutic

purposes. PCNBx provided adequate material in 31/36 cases, giving an overall

sample yield of 86.1%. PCNBx diagnosis was confirmed by surgery in 27/31

patients, giving a sensitivity of 91.6% and a specificity of 87.5%. In 4

patients, the lesions were misdiagnosed by PCNBx. In 5 patients with benign

processes, surgical intervention could have been avoided, according to PCNBx

results. The rate of PCNBx-induced pneumothorax was 11%. Radiologically guided

PCNBx is an easy and safe procedure that can provide important preoperative

diagnostic information and can circumvent the need for exploratory diagnostic

surgery in cases of benign lesions. PCNBx also allows better preoperative

planning in cases of malignancy.

PMID: 11041111 [PubMed - indexed for MEDLINE]

20. Anticancer Drugs. 2000 Feb;11(2):117-21.

Monthly gemcitabine (days 1, 8 and 15) plus cisplatin (days 1-3) in advanced

non-small cell lung cancer: a phase II study.

Merimsky O(1), Wigler N, Greif Y, Schwartz Y, Asna N, Paz J, Mann A, Inbar M.

Author information:

(1)Department of Oncology, Institute of Pulmonology, Tel-Aviv Sourasky Medical

Center, Israel. merimsky@zahav.net.il

On the basis of the reported efficacy of gemcitabine plus cisplatin in patients

with non-small cell lung cancer (NSCLC), this combination has been selected to be

given as our firstline service regimen for advanced or metastatic disease.

Patients recruitment was almost unlimited: no exclusion criteria were made,

except for disease-related Karnofsky's performance status below 50%, the presence

of central nervous system or spinal involvement by uncontrolled metastases, or

creatinine clearance below 50 ml/min. Cisplatin 30 mg/m2/day on days 1-3 and

gemcitabine 1250 mg/m2/day on days 1, 8 and 15 every 4 weeks were given on an

outpatient schedule to consecutive patients with locally advanced or metastatic

NSCLC. Forty-three successive NSCLC patients with histologically or cytologically

proven disease were treated. Adenocarcinoma was diagnosed in 35% of cases,

squamous cell carcinoma in 60% and broncho-alveolar type in 5%. Smoking was

mentioned by 63% of the patients. Numerous medical problems were recorded in 75%

of the patients. Stage IIIB was observed in 10 of 43 patients, while metastatic

disease was found in the rest. All the patients, except for two, were

symptomatic. Two patients achieved complete response (5%) and 16 achieved partial

response (37%), yielding an overall objective response rate of 42%. Minimal

response was observed in seven patients (16%) and disease stabilization in 7%.

Adding the objective response rate to the minimal response and stabilization

rates, the disease-control (progression-free) rate reaches 65%. The time to

progression ranged from 0 to 69 weeks in all the patients. The overall survival

of the group ranged from 4 to 98 weeks, with a median of 45 weeks. Clinical

benefit response was observed mainly in patients who also achieved an objective

response. We conclude that outpatient cisplatin plus gemcitabine combination is

feasible, efficacious and justified in patients with advanced or metastatic

NSCLC.

PMID: 10789594 [PubMed - indexed for MEDLINE]

21. Oncology. 2000 Apr;58(3):210-4.

Primary sarcomas of the central nervous system.

Merimsky O(1), Lepechoux C, Terrier P, Vanel D, Delord JP, LeCesne A.

Author information:

(1)Unit of Bone and Soft Tissue Sarcomas, Department of Medicine, Institut Gustav

Roussy, Villejuif, France. merimsky@zahav.net.il

The medical files of 14 patients with primary brain and spine sarcomas were

retrospectively reviewed. Ten patients had primary brain sarcomas and 4 primary

spinal sarcomas. The tumors probably originated in the brain substance or blood

vessels, in the meninges or in the inner aspect of the skull. The spinal tumors

originated in the nerve roots of the cauda equina and in the spinal substance or

blood vessels. The most common type was angiosarcoma. Removal of the brain tumors

was performed in 95% of the patients. Radiotherapy was delivered to 6 patients

with brain sarcomas and to all patients with primary spinal sarcomas. Metastatic

disease to the lung or pleural effusion was evident in 2 patients who underwent

total removal of their tumors followed by radiation therapy.

PMID: 10765122 [PubMed - indexed for MEDLINE]

22. Cancer. 2000 Jan 15;88(2):364-8.

Metastases to the retroperitoneum in patients with extremity soft tissue sarcoma:

an unusual metastatic pattern.

Lev-Chelouche D(1), Nakache R, Soffer D, Merimsky O, Klausner MJ, Gutman M.

Author information:

(1)Department of Surgery B, Tel Aviv Sourasky Medical Center, Sackler Faculty of

Medicine, Tel Aviv University, Tel Aviv, Israel.

BACKGROUND: Extremity soft tissue sarcoma (STS) metastasizes preferentially to

the lungs via the hematogenous route. Metastases in extrapulmonary sites such as

bone, brain, and subcutaneous tissues are observed less frequently. To the

authors' knowledge, limb STS primarily metastasizing to the retroperitoneum has

not been described to date. The current study reviews the clinical course,

management, and patient prognosis in such a pattern of metastasis.

METHODS: Records of patients with retroperitoneal metastases originating from an

extremity STS between 1994-1998 were reviewed. Patient demographics, primary

tumor site, other tumor sites, local recurrence, distant metastasis, treatment,

and survival were analyzed.

RESULTS: Ten patients were included in the study. All had primary STS of

different histologic types and high histologic grade confined to a lower limb.

The retroperitoneal metastases were diagnosed between 6-120 months (mean, 45

months) after diagnosis of the primary sarcoma. At that time, one patient had

evidence of local recurrence of the primary tumor site, two patients had lung

metastases, and one patient had diffuse bone metastases. Eight patients were

eligible for surgery. In six of these patients the metastases were excised

completely. The median follow up was 12 months. Of the six patients who underwent

complete resection, 3 were alive at last follow-up with no evidence of disease

after 12 months, 14 months, and 24 months, respectively. Two patients with

recurrent retroperitoneal disease and one patient with retroperitoneal and lung

metastases died despite systemic chemotherapy.

CONCLUSIONS: Extremity STS can metastasize hematogenously to the retroperitoneum,

a fact that mandates a high index of suspicion and abdominal imaging studies

during the follow-up of such patients. Retroperitoneal metastases necessitate

aggressive surgical resection to enable prolongation of survival.

PMID: 10640969 [PubMed - indexed for MEDLINE]

23. J Neurooncol. 1999 Mar;42(1):85-92.

Radiation therapy of metastatic spinal cord compression. Multidisciplinary team

diagnosis and treatment.

Kovner F(1), Spigel S, Rider I, Otremsky I, Ron I, Shohat E, Rabey JM, Avram J,

Merimsky O, Wigler N, Chaitchik S, Inbar M.

Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of

Medicine, Tel-Aviv University, Israel. kfelix@iol.co.il

PURPOSE: To evaluate the effectiveness of a multidisciplinary approach to spinal

cord compression (SCC) in accordance with prospective protocol, providing a

uniform approach to diagnosis, decision making concerning optimal treatment

modality in any particular case of SCC, treatment performance and evaluation of

treatment results. The SCC patients treated by radiation therapy are described.

MATERIALS AND METHODS: Patients with SCC were examined and treated by a

multidisciplinary team consisting of a neurologist, radiologist, oncologist,

orthopedic surgeon, and neurosurgeon. Seventy-nine patients for whom radiation

was recommended received a 30 Gy radiation dose to a compression-causing mass and

course of high dose dexamethasone. Three fractions of 5 Gy and 5 fractions 3 Gy

each were delivered by Co60 or 8 MV photon beam in 12 days. Treatment outcome was

essentially evaluated by ambulation capabilities which were considered to be the

main problem of SCC. Changes in other neurologic motor, sensory and autonomic

disturbances were also evaluated.

RESULTS: Seventy-two percent of the patients were already non-ambulatory at

diagnosis. The first symptom was motor deficiency in only 33% of them while in

all other cases it was pain. Ambulation capability was the main prognosticator of

treatment outcome; 90% of patients who were ambulatory before treatment remained

so while 33% of the non-ambulatory patients regained their ability to walk. The

grade of motor disturbance was also an important variable: among the

non-ambulatory patients, 50% of the paretic but only 14% of the plegic ones

became ambulatory. Overall, 51% of the study patients were ambulatory after

undergoing radiation. The ambulatory state after treatment was the main predictor

for survival.

CONCLUSION: Close cooperation of a multidisciplinary team in diagnosis and

treatment according to the above protocol enabled the achievement of good results

of radiation treatment in SCC. Early diagnosis and early treatment should further

enhance therapeutic outcome.

PMID: 10360483 [PubMed - indexed for MEDLINE]

24. Hum Antibodies Hybridomas. 1996;7(4):151-6.

Reactivity to tyrosinase: expression in cancer (melanoma) and autoimmunity

(vitiligo).

Merimsky O(1), Shoenfeld Y, Baharav E, Zigelman R, Fishman P.

Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Petach-Tikva,

Israel.

Anti-tyrosinase antibodies are found in the sera of patients with diffuse

vitiligo, metastatic melanoma and in sera of patients with melanoma and

hypopigmentation (MAH). The autoantigen is tyrosinase itself, the enzyme that

participates in pigment (melanin) formation by both melanocytes and melanoma

cells. The production of autoantibodies in both diseases is associated with the

development of white patches on the patients' skin. The presence of these

autoantibodies in patients with melanoma may suggest a better prognosis.

Cross-antigenicity between melanoma cells and normal melanocytes is most probably

the key mechanism leading to the appearance of MAH. Anti-tyrosinase antibodies

are absorbed by melanocytes and by melanoma cells in all the 3 situations

(melanoma, vitiligo, MAH). However, since the production of antibodies in

vitiligo exceeds that in melanoma or MAH, the antibodies are detected in

significantly higher levels only in vitiligo. It is suggested here that

anti-tyrosinase antibodies may be responsible, or at least participate in

destruction of normal melanocytes during the immune response to melanoma

antigens. This mechanism may be responsible for the phenomenon of MAH in patients

with melanoma, and for the formation of the autoimmune vitiligo. Anti-tyrosinase

antibodies may serve for two clinical applications. One is a marker for

monitoring and follow up of patients with melanoma treated by immune therapy. The

second is active (or passive) immunotherapy. We have recently shown that C57BL/6J

mice immunized with tyrosinase generated a high titer of antityrosinase

antibodies, and following the inoculation of melanoma cells developed lower

number of lung metastases, compared to the unvaccinated control group.

PMID: 9140726 [PubMed - indexed for MEDLINE]

25. J Surg Oncol. 1995 Aug;59(4):239-42.

Tumor ploidy as a risk factor for disease recurrence and short survival in

surgically-treated Dukes' B2 colon cancer patients.

Nori D(1), Merimsky O, Samala E, Saw D, Cortes E, Chen E, Turner JW.

Author information:

(1)Department of Radiation Oncology, New York Hospital Medical Center of Queens,

Flushing 11355-5095, USA.

The risk factors for colon cancer recurrence following a curative intent surgery

include the presence of metastatic disease, the tumor location and size, number

of positive lymph nodes, the presence of adhesions, perforation, bowel

obstruction, depth of invasion, histological grade, percentage of S-phase

content, and cell kinetic profile. The DNA content of colon cancers in 20 Dukes'

B2 patients in follow-up evaluation at our center, who relapsed, either locally

or systemically following surgical treatment was measured by image analysis. The

data were pair-matched for age, sex, tumor site, and grade with 20 Dukes' B2

patients who had no evidence of disease. Aneuploidy occurred in 16 (80%) patients

with recurrence, as compared with only in 8 (40%) in the control group.

Aneuploidy was associated with significantly higher tumor recurrence rate (P =

0.024) and shorter overall survival (P < 0.002). Our data may point out a

possible indication for systemic adjuvant chemotherapy in Dukes' B2 colon cancer

patients who have aneuploid tumors on image analysis. This warrants further

investigation in a prospective controlled randomized study.

PMID: 7630171 [PubMed - indexed for MEDLINE]

26. Cancer Immunol Immunother. 1993 Jul;37(1):61-6.

Recombinant interferon alpha-2a in combination with dacarbazine in the treatment

of metastatic malignant melanoma: analysis of long-term responding patients.

Ron IG(1), Inbar MJ, Gutman M, Merimsky O, Chaitchik S.

Author information:

(1)Department of Oncology, Tel-Aviv-Elias Sourasky Medical Center, Sackler

Faculty of Medicine, Tel-Aviv University, Israel.

Thirty-four evaluable patients with metastatic malignant melanoma were entered

into a phase-II study designed to assess the response rate and analyze the

long-term therapeutic efficacy of recombinant interferon (rIFN) alpha-2a and

dacarbazine. Patients received 14 days of daily subcutaneous r-IFN alpha-2a (3 x

10(6) IU/day), followed by 9 x 10(6) IU on alternate days, as long as objective

response lasted, in combination with i.v. dacarbazine started on day 7 (400

mg/m2) and repeated every 21 days (dacarbazine doses were escalated to 800

mg/m2). In 11 patients, 6 complete (17.6%) and 5 partial (14.7%) responses were

seen, with an overall response rate of 32.3% (95% confidence interval: 16%-48%).

The median survival time of the responding patients was significantly better than

that of patients with progressive disease (P = 0.01) and the median response time

of the patients showing complete response was longer than that of the partially

responding patients (14 and 7 months respectively, P = 0.06).

PMID: 8513453 [PubMed - indexed for MEDLINE]

27. Eur J Cancer. 1993;29A(3):481-2.

Fotemustine-dacarbazine combinations in the treatment of metastatic melanoma.

Merimsky O, Chaitchik S.

PMID: 8398358 [PubMed - indexed for MEDLINE]

28. Anticancer Drugs. 1992 Aug;3(4):375-7.

Cisplatin-related Lhermitte's sign.

Inbar M(1), Merimsky O, Wigler N, Chaitchik S.

Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Israel.

The sensation of a sudden electrical impulse travelling along the spine to the

legs and feet on flexion of the neck has been known as Lhermitte's sign.

Lhermitte's sign, as part of cisplatin-related neurotoxicity, was observed in

four patients, with ovarian or lung cancer, simultaneously with peripheral

neuropathy, after a dose of 375-700 mg/m2. The dose intensity (DI) of cisplatin

in our patients ranged from 12.5 to 26.9 mg/m2/week. No direct relationship was

found between DI and the timing of Lhermitte's sign. Other relevant causes for

this sign were ruled out. The mechanism responsible for the development of

Lhermitte's sign is unclear. Interruption of treatment with cisplatin may not

prevent the appearance of Lhermitte's sign. In most of the reported cases in the

literature this sign developed after the end of cisplatin courses.

PMID: 1421433 [PubMed - indexed for MEDLINE]

29. Mol Biother. 1990 Sep;2(3):155-9.

Phase II study of recombinant interferon alpha-C in patients with metastatic

renal cell carcinoma.

Merimsky O(1), Inbar M, Merimsky E, Kovner F, Spitzer E, Laufer R, Braf Z,

Chaitchik S.

Author information:

(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Sackler School of

Medicine, Tel-Aviv University, Israel.

Recombinant interferon alpha-C is a new strain of the alpha interferon family. It

was given to 33 patients with measurable metastatic renal cell carcinoma of whom

31 were evaluable. Protocol consisted of 3 million U/d for 2 weeks, then 3

million U/m2 every other day until progression. No complete response was

observed. Three patients (9.7%) had partial response for a mean duration of 5.6

months and eight patients (25.8%) were stabilized for a mean of 4.3 months.

Responsive sites were mainly lung, bone, and kidney, while side effects were

generally mild. better results were observed in previously nephrectomized

patients who had not received chemotherapy or hormonotherapy for recurrent or

metastatic disease (p less than 0.05), and also in patients with a brief

disease-free interval and short delay from presenting symptoms of the primary

tumor until interferon treatment (p less than 0.05). Median survival was

significantly longer in responders than in progressors (p less than 0.05). We

suggest that the efficacy of recombinant interferon alpha-C in a low-dose regime

versus other types of interferon as first-line therapy for inoperable,

metastatic, or locally recurrent renal cell carcinoma should be investigated in a

prospective, controlled, randomized study.

PMID: 2222899 [PubMed - indexed for MEDLINE]

30. Tumori. 1990 Aug 31;76(4):407-9.

Recurrent solitary metastasis of renal cell carcinoma in skeletal muscles.

Merimsky O(1), Levine T, Chaitchik S.

Author information:

(1)Department of Oncology, Ichilov Hospital Tel-Aviv Medical Center, Israel.

Metastatic carcinoma to skeletal muscle is uncommon and may originate from

breast, colon, lung, pancreas and other sources. Recurrent solitary metastases of

renal cell carcinoma in the biceps femori and gluteus muscles are described in a

69 year-old man. The tendency of metastases to occur merely in muscles could not

be explained in our case. The relative immunity of muscle to the metastatic

process should be further investigated.

PMID: 2399572 [PubMed - indexed for MEDLINE]

31. J Urol (Paris). 1986;92(9):617-9.

Spontaneous breakage of a double pigtail stent and bladder stone formation.

Papo J, Waizbard E, Merimsky E.

Five years after prostate resection and hormonal treatment for carcinoma of

prostate a 76 year old patient presented with bone and lung metastases and

dilatation of left upper collecting system. After castration a double J stent was

inserted in the ureter. Two years later he was admitted for alteration in general

condition related to cholecystitis. A standard radiograph showed the catheter

fractured into four pieces, although no urinary signs had been reported during

this 2-year period. Cholecystectomy was performed and the patient reviewed 6

weeks later: urography showed good functioning of the kidney and the absence of

obstruction of the collecting system. The process of fragmentation continued and

a bladder calculus developed on fragments falling into bladder: it was extracted

by lithotripsy. The patient was asymptomatic and refused further investigation or

treatment. This case is one of several reported in the literature and silicone or

C-flex should be substituted for polyethylene.

PMID: 3819464 [PubMed - indexed for MEDLINE]

פרופסור עפר מרימסקי

מומחה באונקולוגיה קלינית וקרינתית

Русский

English