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Novel combination chemotherapy with topotecan, doxorubicin and vincristine (TAV) in patients with advanced lung cancer.

7251 Background: Topotecan has a role in the second-line therapy of small cell lung cancer (SCLC), and has activity in advanced non-small cell lung cancer (NSCLC). The objective of this study was to determine the safety and maximum tolerated dose (MTD) of a novel combined chemotherapy regimen: topotecan (T), doxorubicin [Adriamycin (A)], and vincristine (V), for the development of Phase II trial.


METHODS
Patients (pts) with advanced SCLC or NSCLC who had incurable disease were enrolled.Pts should have failed palliative chemotherapy first, unless they have extensive disease (ED). The schema used for therapy was: T was escalated from 0.75 mg/m2 days 1-5 every four weeks; fixed doses of V and A were given at 1 mg/m2 days 1 and 5, and 30 mg/m2 day five only, respectively. Each cohort had three pts. Dose limiting toxicity (DLT) was defined as grade 4 hematological toxicity persisting for more than 7 days or any grade 4 non-hematological toxicity.


RESULTS
Fifteen pts were enrolled: 8 males and 7 females, with a median age of 53 years (35-72 years). Thirteen pts were white, and 11 had a Hispanic origin. Nine pts had NSCLC and six SCLC. A total of 36 cycles of TAV were given. The combination was well tolerated. No DLT were seen in the 0.75 mg/m2 or 1 mg/m2 cohorts. Only 1/6 pts developed DLT in the 1.25 mg/m2 cohort with grade 4 neutropenia and thrombocytopenia. We stopped accrual in the 1.5 mg/m2 cohort; we did not consider necessary to increase the dose of T because this is the dose commonly used as a single agent. From the 9 pts with NSCLC: all were stage IV, 4/9 had received at least 2 lines of palliative chemotherapy, 4/9 had failed radiation, and 1/9 pt had a sustained PR (11%). Among the 6 pts with SCLC: 5 had ED (3 already treated with chemotherapy), and one with limited disease that had relapsed. The overall response rate was 2/6 (33.3%): 1 CR and 1 PR, with another patient who attained SD (16.7%).


CONCLUSIONS
The MTD for T is close to 1.25 mg/m2 for this combination based on our experience and the data in the literature. The activity seen in ED-SCLC (50% clinical benefit) may justify the development of a Phase II trial in this setting. [Table: see text].