A phase II study of picoplatin (pico) as second-line therapy for patients (pts) with small cell lung cancer (SCLC) who have resistant or refractory disease or have relapsed within 180 days of completing first-line, platinum (plat)-containing chemotherapy

Abstract

7722 Background: Pico is a sterically hindered plat analogue designed to overcome plat resistance with improved safety and efficacy. In >600 pts pico had single-agent activity in lung, prostate, ovarian and other malignancies with rare significant nephro-, oto-, or neurotoxicity (∼2% grade 3 and 0% grade 4). In a previous phase 2 study of single agent pico as 2nd line therapy in SCLC, 4 of 48 pts (8%) had a partial response and 21 (44%) stable disease. Median survival was 27.0 (95% CI = 16–35) wks. This multi-center phase 2 trial was designed to confirm the activity of pico as 2nd line monotherapy for plat-resistant SCLC. Methods: Pts with SCLC who either 1) failed or progressed through 1st line plat-containing chemo (refractory disease), or 2) initially responded to 1st line plat-containing chemo and then relapsed/ progressed within 3 months (resistant disease), or 3) initially responded and then relapsed/progressed between 90 to 180 days (sensitive, relapsed 90 to 180 days), had measurable disease and ECOG PS 0–2 were treated with pico, 150 mg/m2 iv over1–2 hrs, q 21 days. Tumor response was assessed q 6 wks. Adverse events (AEs) were graded using the NCI CTCAE. Results: 77 pts received pico (45 refractory, 27 resistant, 5 sensitive). The median number of cycles received was 2 (mean = 2.9). The most frequently reported AEs of any severity were thrombocytopenia (39% of pts), anemia (35%), neutropenia (22%), nausea (20%), emesis (14%) and dyspnea (25%). Neutropenic fever occurred in 1 pt; there were no treatment related deaths. One pt had grade 3 neuropathy; there was no grade 3 or 4 ototoxicity or nephrotoxicity. Median overall survival is 28.1 (95% CI = 26–37) wks. Median progression free survival is 9.3 (95% CI = 7–12) wks. Of 63 pts with at least 1 post-treatment assessment of disease status, 33 (52%) had stable disease. Conclusion: Median survival compares favorably with other therapeutic options and toxicity is reduced in pico treated SCLC pts who have failed prior plat-containing first-line chemo or who have progressed within 180 days of first-line chemo. A phase III trial to confirm these results has been initiated. No significant financial relationships to disclose.