Randomized phase II study of picoplatin in combination with 5-fluorouracil and leucovorin (FOLPI) as a neuropathy-sparing alternative to modified FOLFOX-6 as first-line therapy for colorectal cancer (CRC)

• Published in: Journal of clinical oncology Vol. 27; no. 15_suppl; p. 4026
• Main Authors: Earhart, R., Cheporov, S., Gladkov, O., Biakhov, M., Breitz, H., De Jager, R.
• Format: Journal Article
• Language: English
• Published: 20-05-2009
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2009.27.15_suppl.4026

Abstract only 4026
Background: Picoplatin (Pico) was designed to overcome platinum resistance and has the potential for improved safety compared to other platinum agents. FOLFOX (5-FU, LV, oxaliplatin [oxali]) treatment for advanced CRC has dose-limiting oxali- related neurotoxicity. The incidence of grade (G) 3–4 neurotoxicity with single-agent Pico across studies was <2%, suggesting that Pico may provide a neuropathy-sparing alternative to oxali. A Phase I trial identified the Pico MTD at 150 mg/m
2
when infused Q4W with Q2W FU/LV. The present study evaluates Pico when administered Q4W with Q2W FU and LV (FOLPI) vs. modified (m) FOLFOX-6 (FOLFOX) as 1st line treatment for patients (pts) with advanced CRC. Methods: Each pt received LV and infusional FU per mFOLFOX-6 Q2W. Pts with no prior chemotherapy for advanced CRC received Pico Q4W (150 mg/m
2
) or oxali Q2W (85 mg/m
2
). Tumor response was assessed by RECIST using CT scans. Adverse events (AEs) were assessed with CTCAE. Neuropathy was assessed using the FACT-Neurotoxicity questionnaire and by a neurologist blinded to treatment. Results: 101 pts were randomized (50 to FOLPI, 51 to FOLFOX). Pts have received 213 (median 4, max 11) 4-week cycles of FOLPI and 414 (median 8, max 21) 2-week cycles of FOLFOX. Median dose intensity of Pico = 28 mg/m
2
/wk (range 19–44); mean relative dose intensity = 77%. Median dose intensity of oxali = 36 mg/m
2
/wk (range 28–43); mean relative dose intensity = 86%. Neurotoxicity was observed in 65% of pts on FOLFOX (10% G 3/4) and 28% of pts on FOLPI (no G 3/4). Most frequent G 3/4 AEs on FOLPI were neutropenia (60%), thrombocytopenia (40%) and anemia (14%). In the FOLFOX arm, other than neuropathy, the most frequent G 3/4 AEs were neutropenia (20%) and thrombocytopenia (12%). Disease control (CR+PR+SD) was 76% for FOLPI and 76% for FOLFOX. In the FOLPI arm there were 1 CR (2%) and 11 PR (22%). In the FOLFOX arm there were no CRs and 13 PR (26%). Conclusions: In this ongoing trial, FOLPI with Pico Q4W shows comparable disease control as measured by RECIST compared to FOLFOX. Neurotoxicity was less frequent and less severe in the FOLPI arm compared to the FOLFOX arm. Pico therefore may be a neuropathy-sparing alternative to oxaliplatin in CRC.
[Table: see text]