Randomized Phase II Trial of Sequential Chemotherapy in Advanced Non-Small Cell Lung Cancer (SWOG 9806)

Abstract

Purpose: Improving chemotherapeutic efficacy in nonsmall cell lung cancer (NSCLC) will require the development of new drugs or new strategies to better use currently available agents. Sequential administration offers an opportunity to increase drug diversity while maintaining dose intensity. On the basis of the data indicating the activity of taxanes as second-line therapy and the lack of efficacy for more than three cycles of platinum-based therapy, this randomized Phase II study tested the concept of planned sequential chemotherapy in advanced NSCLC.Experimental Design: Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0 -1 and normal organ function were eligible. Therapy: arm 1, carboplatin (area under the curve ‫؍‬ 5.5 mg/ml ؋ min day 1) and gemcitabine (1000 mg/m 2 days 1 and 8 every 21 days ؋ 3) followed by paclitaxel (225 mg/m 2 every 21 days ؋ 3) or arm 2, cisplatin (100 mg/m 2 day 1), vinorelbine (25 mg/m 2 days 1 and 8 every 21 d ؋ 3) followed by docetaxel (75-100 mg/m 2 every 21 days ؋ 3). Results: Two-hundred four patients were accrued, of whom, 178 were eligible and evaluable. Eighty percent of patients were stage IV on arm 1 and 85% on arm 2. Response rates were 21 and 28% on arms 1 and 2, respectively. Median, 1-year and 2-year survivals were 9 months, 34 and 13%, and 9 months, 36 and 8%, on arms 1 and 2, respectively.Conclusions: Sequential therapy, as used in this study, resulted in comparable efficacy to previous Southwest Oncology Group trials of two drug combinations in this population; however, it failed to meet criteria for further study.

Gemcitabine and vinorelbine followed by docetaxel in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial of nonplatinum sequential triplet combination chemotherapy (JMTO LC00-02)

“…Recently, Edelman et al (2001a) reported the results of phase II study for sequential combination chemotherapy consisting of carboplatin and GEM followed by paclitaxel showed modest activity (overall response: 31%, median survival time: 9.5 months). Based on the results of this study, Southwest Oncology Group (SWOG) has completed a randomised phase II trial of two sequential combinations (CDDP/VNR followed by DOC vs carboplatin/GEM followed by paclitaxel) and reported that both arms had comparable activity (response rate: 21 and 28%, 1-year survival: 32 and 31%) (Edelman et al, 2001b). The concept of this SWOG study which involved a doublet followed by taxane, is similar to that of the present study.…”

Triplet Platinum-based Combination Sequential Chemotherapy Improves Survival Outcome and Quality of Life of Advanced Non-small Cell Lung Cancer Patients

“…Chemotherapy with platinum-based regimens for more than 6 cycles was usually considered unendurable (Edelman et al, 2004;Belani et al, 2006). However, in our study, we found that the myelosuppression toxicity remained generally tolerable during the whole treatment with G-CSF support.…”

First- and second-line therapy for advanced nonsmall cell lung cancer

“…Two phase II trials have been published on sequential chemotherapy (table 10) [94,95]. The ELCWP completed a large phase III trial [95] where patients without disease progression after three courses of cisplatin-based chemotherapy were randomised between further platinum-based chemotherapy or paclitaxel with crossover at the time of progression.…”