TITLE

Gemcitabine and vinorelbine in patients with advanced lung cancer: preclinical studies and report of a phase I trial

AUTHOR(S)
Herbst, Roy S.; Lynch, Cathleen; Vasconcelles, Michael; Teicher, Beverly A.; Strauss, Gary; Elias, Anthony; Anderson, Ian; Zacarola, Patrick; Dang, Nam H.; Leong, Traci; Salgia, Ravi; Skarin, Arthur T.; Herbst, R S; Lynch, C; Vasconcelles, M; Teicher, B A; Strauss, G; Elias, A; Anderson, I; Zacarola, P
PUB. DATE
August 2001
SOURCE
Cancer Chemotherapy & Pharmacology;Aug2001, Vol. 48 Issue 2, p151
SOURCE TYPE
Academic Journal
DOC. TYPE
journal article
ABSTRACT
Purpose: This study was designed to assess the efficacy of gemcitabine plus vinorelbine using the mouse Lewis lung carcinoma model and to translate this regimen to a phase I clinical study of these two agents in patients with advanced lung cancer.Materials and Methods: Using the mouse Lewis lung cancer model, employing growth delay and isobologram analysis, we demonstrated that gemcitabine, in combination with vinorelbine, produced additive activity with little increased toxicity over a wide range of doses. At the highest dose level studied, antagonism was observed. Based on these results, we initiated a phase IGemcitabine and vinorelbine in patients with advanced lung cancer: preclinical studies and report of a phase I trial study of this combination at the Dana Farber Cancer Institute (DFCI) in patients with untreated or once pretreated non-small-cell lung cancer (NSCLC) or once pretreated small-cell lung cancer (SCLC). Vinorelbine (given in an intravenous bolus) and gemcitabine (given in a 30-min infusion) were initially administered to patients at a dose of 15 mg/m2 and 500 mg/m2, respectively, on days 1, 8, and 15 of a 28-day cycle. Seven dose levels were subsequently explored over the course of the study. There was no intrapatient dose escalation.Results: From November 1996 to March 1998, 40 patients were enrolled: 32 had NSCLC, 5 had SCLC and 3 had mixed disease (both SCLC and NSCLC). The patients were evenly divided by gender, the median age was 58 years (range 38 to 73 years), and the median ECOG performance status was 1 (range 0 to 2). All patients had normal renal and hepatic function and none had previously received gemcitabine or vinorelbine. Toxic reactions included mild to moderate fatigue, nausea, constipation, and, most significantly, neutropenia and thrombocytopenia. Phlebitis was a major problem when central venous lines were not used with 15% grade 1/2 events. The day-15 dose was held in 43% of patients at the expanded dose. No true maximum tolerated dose was reached after completion of seven dose levels. Dose level 4 (22.5 mg/m2 vinorelbine and 1,000 mg/m2 gemcitabine) was chosen for expansion and future study due to the potential increased ability of patients to receive the full doses on time.Conclusions: We conclude that this drug combination and dosage are feasible and have potential as either a front- or second-line chemotherapeutic regimen for advanced lung cancer, and phase II/III trials should be performed. However, hematologic toxicities, as found in this study, could probably be reduced with treatment on days 1 and 8 every 21 days, and current literature would suggest this to be the preferred schedule.
ACCESSION #
15653465

 

Related Articles

  • Dose escalation study of irinotecan combined with carboplatin for advanced non-small-cell lung cancer. Takeda, Koji; Negoro, Shunichi; Takifuji, Nobuhide; Nitta, Takashi; Yoshimura, Naruo; Terakawa, Kazuhiko; Fukuoka, Masahiro; Takeda, K; Negoro, S; Takifuji, N; Nitta, T; Yoshimura, N; Terakawa, K; Fukuoka, M // Cancer Chemotherapy & Pharmacology;Aug2001, Vol. 48 Issue 2, p104 

    From December 1994 to July 1997, we conducted a dose escalation study of irinotecan combined with carboplatin in 17 patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum tolerated dose and the dose-limiting toxicities. Irinotecan was administered intravenously over...

  • First line chemotherapy with planned sequential administration of gemcitabine followed by docetaxel in elderly advanced non-small-cell lung cancer patients: a multicenter phase II study. Tibaldi, C.; Vasile, E.; Antonuzzo, A.; Di Marsico, R.; Fabbri, A.; Innocenti, F.; Tartarelli, G.; Amoroso, D.; Andreuccetti, M.; Dico, M. Lo; Falcone, A. // British Journal of Cancer;2/5/2008, Vol. 98 Issue 3, p558 

    This multicenter phase II study evaluated, in chemonaive patients with stage IIIB–IV NSCLC, age 70 and with a performance status 0–2, the activity, efficacy and tolerability of planned sequential administration of gemcitabine 1200 mg m−2 on days 1 and 8 every 3 weeks...

  • Phase II study of gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer. Wang, Lin; Huang, Ming; Zhang, Guo; Xu, Nong; Wu, Xiu // Cancer Chemotherapy & Pharmacology;Oct2007, Vol. 60 Issue 4, p601 

    To evaluate the efficacy and safety of gemcitabine in combination with carboplatin at standard rate or fixed dose rate infusion in patients with advanced non-small-cell lung cancer (NSCLC). In this prospective study, patients with chemonaive advanced NSCLC were randomized to receive gemcitabine...

  • Phase II study of nedaplatin and irinotecan with concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer. Oshita, F.; Ohe, M.; Honda, T.; Murakami, S.; Kondo, T.; Saito, H.; Noda, K.; Yamashita, K.; Nakayama, Y.; Yamada, K. // British Journal of Cancer;10/26/2010, Vol. 103 Issue 9, p1325 

    Background: Current international guidelines recommend the use of platinum-based chemotherapy with thoracic radiotherapy (TRT) for patients with locally advanced non-small-cell lung cancer (NSCLC).Methods: Patients with unresectable stage IIIA or IIIB NSCLC were treated...

  • Fondaparinux was not inferior to unfractionated heparin for symptomatic pulmonary embolism: COMMENTARY. Gould, Michael K. // ACP Journal Club;May/Jun2004, Vol. 140 Issue 3, p68 

    Fondaparinux is a synthetic pentasaccharide that exerts its anticoagulant effect by direct and specific inhibition of factor Xa. Unlike unfractionated heparin (UFH), it has a more predictable dose-response relation, does not require laboratory monitoring in most circumstances, and can be given...

  • CD56-Positive Acute Lymphoblastic Leukemia. Matano, Sadaya; Terahata, Shintaro; Nakamura, Shigeo; Kobayashi, Kazumi; Sugimoto, Tatshuho // Acta Haematologica;2005, Vol. 114 Issue 3, p160 

    We report a patient with lung cancer who developed CD56-positive acute lymphoblastic leukemia. He was referred to our hospital for thrombocytopenia. Atypical cells were found in the blood and the bone marrow. These cells were immunophenotypically positive for CD3ε, CD56, and terminal...

  • Oxaliplatin-induced immune mediated thrombocytopenia. Beg, Muhammad S.; Komrokji, Rami S.; Ahmed, Kashif; Safa, Malek M. // Cancer Chemotherapy & Pharmacology;Oct2008, Vol. 62 Issue 5, p925 

    Oxaliplatin is a third generation platinum compound used in patients with advanced colorectal carcinoma. Recently, the mechanism of a rare drug-induced immune thrombocytopenia in patients receiving oxaliplatin has been described. This complication is caused by oxaliplatin-dependent antibodies...

  • A phase I study of erlotinib in combination with gemcitabine and radiation in locally advanced, non-operable pancreatic adenocarcinoma. A. Duffy; J. Kortmansky; G. K. Schwartz; M. Capanu; S. Puleio; B. Minsky; L. Saltz; D. P. Kelsen; E. M. OReilly // Annals of Oncology;Jan2008, Vol. 19 Issue 1, p86 

    Purpose: To determine the maximum tolerated dose (MTD) of erlotinib when administered concurrently with twice weekly gemcitabine and radiation therapy (RT) for locally advanced pancreatic cancer, assess the safety and toxicity profile of this combination and secondarily evaluate response, time...

  • A Phase II Study of the Docetaxel- Ifosfamide-Carboplatin Combination in Advanced Non-Small-Cell Lung Cancer. Kosmas, Christos; Tsavaris, Nicolas; Koutras, Aggelos; Makatsoris, Thomas; Mylonakis, Nicolas; Tzelepis, George; Dimitrakopoulos, Antonis; Spyropoulos, Konstantinos; Polyzos, Aristidis; Karabelis, Athanasios; Kalofonos, Haralambos P. // Oncology;2005, Vol. 69 Issue 4, p333 

    Purpose: In the present phase II study we evaluated the docetaxel-ifosfamide-carboplatin (DICb) combination in the outpatient setting in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Patients with advanced NSCLC (stages IIIB/IV), WHO performance status (PS) <2,...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics