מאמרים בתחום סרטן הריאות
1. Target Oncol. 2015 Jun;10(2):255-65. doi: 10.1007/s11523-014-0336-7. Epub 2014
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.
(1)LungenClinic Grosshansdorf, Woehrendamm 80, 22927, Grosshansdorf, Germany,
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.
(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
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.
(1)Department of Oncology, Institute of Oncology, Sheba Medical Center, Tel
Hashomer, 52621, Ramat Gan, Israel, firstname.lastname@example.org.
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
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
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
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
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,
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
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,
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
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).
Copyright © 2014 Elsevier Ltd. All rights reserved.
PMID: 24331154 [PubMed - indexed for MEDLINE]
5. Br J Radiol. 2013 Aug;86(1028):20130258. doi: 10.1259/bjr.20130258. Epub 2013 May
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.
(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.
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
Kushnir I(1), Merimsky O.
(1)Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv 64239,
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.
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.
(1)Division of Oncology, Tel Aviv Medical Center, Tel-Aviv 64239, Israel.
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.
(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.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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.
(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
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
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,
(1)Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Sackler Faculty
of Medicine, Tel Aviv University, 6 Weizman Street, Tel Aviv 64239, Israel.
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
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.
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.
(1)Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel Aviv Sourasky
Medical Center, Tel Aviv University, Tel Aviv, Israel.
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.
(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
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
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.
(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,
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
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.
(1)Unit of Soft Tissue and Bone Oncology, Tel Aviv Sourasky Medical Center, Tel
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.
(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239,
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
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,
(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv University,
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
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
PMID: 11583195 [PubMed - indexed for MEDLINE]
18. Oncology. 2001;60(1):55-9.
Is forequarter amputation justified for palliation of intractable cancer
Merimsky O(1), Kollender Y, Inbar M, Lev-Chelouche D, Gutman M, Issakov J, Mazeh
D, Shabat S, Bickels J, Meller I.
(1)Department of Oncology, The Tel-Aviv Sourasky Medical Center, Tel-Aviv,
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
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.
(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.
(1)Department of Oncology, Institute of Pulmonology, Tel-Aviv Sourasky Medical
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
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.
(1)Unit of Bone and Soft Tissue Sarcomas, Department of Medicine, Institut Gustav
Roussy, Villejuif, France.
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.
Copyright 2000 S. Karger AG, Basel
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.
(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.
Copyright 2000 American Cancer Society.
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.
(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of
Medicine, Tel-Aviv University, Israel.
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
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
Merimsky O(1), Shoenfeld Y, Baharav E, Zigelman R, Fishman P.
(1)Department of Oncology, Tel-Aviv Sourasky Medical Center, Petach-Tikva,
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.
(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.
(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.
(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,
(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.
(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]