Paclitaxel (PTX) as second line treatment in patients (pts) with small cell lung cancer (SCLC) refractory to carboplatin - etoposide: A multicenter phase II study

Abstract

7211 Background: pts non-responding to 1st line chemotherapy or relapsing within 3 months (m) of confirmed prior response are considered refractory to treatment and candidate for phase II trials, as second line therapy in refractory SCLC is disappointing (Huisman, 1999). The present study aimed to assess the activity and toxicity of single agent PTX in pts refractory to first line carboplatin and etoposide. Methods: Eligible pts had to present with cytological or histological proof of SCLC, at least 1 measurable lesion, WHO PS ≤ 2, age ≥ 18 years, and adequate renal, hepatic and bone marrow function. After informed consent, pts were treated in first line with carboplatin AUC 6 on d1 or 100 mg/m2 on d1–3 and etoposide 120 mg/m2 on d1–3, q 4w for up to 6 cycles Refractory pts were treated with PTX 200 mg/m2 as a 3 h infusion q 3w for up to 6 cycles, after adequate premedication. Appropriate dose reductions were made according to toxicity. The prophylactic use of CSF's was not allowed. PCI was optional and thoracic irradiation mandatory in LD pts obtaining response. Response and toxicity were defined using WHO and NCI-CTC criteria, respectively. The study was powered to detect a true response rate of PTX ≥ 20% using a 2 step design according to Gehan with a 2-sided alpha error of 0.05 and a beta error of 0.1. Results: between October 1998 and August 2001, 93 pts with the following characteristics started 1st line therapy: male 98%, median age 66 years (range 39–88), WHO PS 0/1/2: 18/75/7%, Extensive stage 55%. 44 refractory pts, of whom 52% non-responders to 1st line, received PTX. Mean number of PTX cycles was 3 (range 1–6). The ORR was 20% (95%CI 11–29%). Toxicity was evaluable in 40 pts:grade ¾ (%): fatigue 13/-, dyspnea 5/-, neuropathy 8/-, arthralgia/myalgia 8/-, anemia 5/-, febrile neutropenia: 23% . No toxic deaths were observed, although 3 pts died of disease progression during treatment. Median OS and TTP on PTX were 4 and 3 m, respectively. Conclusions: the observed activity of PTX in pts with refractory SCLC looks promising, provided febrile neutropenia can be avoided/prevented. No significant financial relationships to disclose.