Randomized Phase II trial of paclitaxel and carboplatin followed by gemcitabine switch-maintenance therapy versus gemcitabine and carboplatin followed by gemcitabine continuation-maintenance therapy in previously untreated advanced non-small cell lung cancer.

Abstract

BACKGROUND:

In recent years, maintenance chemotherapy is increasingly being recognized as a new treatment strategy to improve the outcome of advanced non-small cell lung cancer (NSCLC). However, the optimal maintenance strategy is still controversial. Gemcitabine is a promising candidate for single-agent maintenance therapy because of little toxicity and good tolerability. We have conducted a randomized phase II study to evaluate the validity of single-agent maintenance chemotherapy of gemcitabine and to compare continuation- and switch-maintenance.

METHODS:

Chemonaïve patients with stage IIIB/IV NSCLC were randomly assigned 1:1 to either arm A or B. Patients received paclitaxel (200 mg/m2, day 1) plus carboplatin (AUC 6 mg/mL/min, day 1) every 3 weeks in arm A, or gemcitabine (1000 mg/m2, days 1 and 8) plus carboplatin (AUC 5 mg/mL/min, day1) every 3 weeks in arm B. Non-progressive patients following 3 cycles of induction chemotherapy received maintenance gemcitabine (1000 mg/m2, days 1 and 8) every 3 weeks.

TRIAL REGISTRATION:

UMIN000008252) RESULTS: The study was stopped because of delayed accrual at interim analysis. Of the randomly assigned 50 patients, 49 except for one in arm B were evaluable. Median progression-free survival (PFS) was 4.6 months for arm A vs. 3.5 months for arm B (HR = 1.03; 95% CI, 0.45-2.27; p = 0.95) and median overall survival (OS) was 15.0 months for arm A vs. 14.8 months for arm B (HR = 0.79; 95% CI, 0.40-1.51; p = 0.60), showing no difference between the two arms. The response rate, disease control rate, and the transit rate to maintenance phase were 36.0% (9/25), 64.0% (16/25), and 48% (12/25) for arm A vs. 16.7% (4/24), 50.0% (12/24), and 33% (8/24) for arm B, which were also statistically similar between the two arms (p = 0.13, p = 0.32, and p = 0.30, respectively). Both induction regimens were tolerable, except that more patients experienced peripheral neuropathy in arm A. Toxicities during the maintenance phase were also minimal.

CONCLUSION:

Survival and overall response were not significantly different between the two arms. Gemcitabine may be well-tolerable and feasible for maintenance therapy.

• Authors: Seigo Minami, Takashi Kijima, Takayuki Shiroyama, Kohei Okafuji, Tomonori Hirashima, Junji Uchida, Fumio Imamura, Tadashi Osaki, Takeshi Nakatani, Yoshitaka Ogata, Suguru Yamamoto, Yoshinobu Namba, Tomoyuki Otsuka, Isao Tachibana, Kiyoshi Komuta, Ichiro Kawase
• Journal: BMC research notes (BMC Res Notes) Vol. 6 Pg. 3 (Jan 03 2013) ISSN: 1756-0500 [Electronic] England
• PMID: 23281805 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Deoxycytidine
• Carboplatin
• Paclitaxel
• Gemcitabine

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Humans
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Paclitaxel (administration & dosage)
• Gemcitabine