Picoplatin Effective for CRC with Less Neuropathy

Picoplatin can be as effective as oxaliplatin as an initial treatment for advanced colorectal cancer but has less neuropathy.

Updated information comparing picoplatin in combination with 5-FU and leucovorin (FOLPI) to the standard oxaliplatin treatment (FOLFOX) found similar response rates.  About half of patients on both treatments were alive a year later.  However, there was significantly less neuropathy overall with FOLPI and no severe neuropathy.

FOLPI did have substantially more serious problems with lowered blood counts than FOLFOX. 

Information from 100 patients randomized to receive either FOLPI or FOLFOX for metastatic colorectal cancer was reported during the poster session at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics meeting in Boston on Tuesday, November 17.

Three out of four patients in both study arms had disease control — 73 percent of patients on FOLPI had either a complete response, partial response, or stable disease, while 76 percent of FOLFOX patients had similar results.  A year after beginning treatment, 52 percent of FOLPI patients were alive compared to 55 percent of those who got FOLFOX.

Neuropathy was evaluated using a patient questionnaire and by a neurologist who didn’t know which treatment patients were receiving.

Serious side effect profiles were quite different between the two treatment regimens. While there was significantly less neuropathy overall and no severe neuropathy on FOLPI, the picoplatin combination led seriously lowered blood counts in more than half of all patients.  Grade 3 or 4 adverse events were:

• neutropenia in 57 percent of FOLPI compared to 22 percent with FOLFOX.
• lowered platelets (thrombocytopenia)  in 43 percent of FOLPI compared to12 percent of  FOLFOX
• anemia in 22 percent of FOLPI compared to none in FOLFOX
• neuropathy in no FOLPI patients compared to 16 percent of FOLFOX

One patients in the FOLPI arm was treated for a fever associated with neutropenia but recovered and went on to have a complete response.

One in five patients on both study arms had to stop treatment because of side effects, most often neuropathy for FOLFOX (10 percent) and lowered blood counts for FOLPI (14 percent).

FOLPI required considerably more support to regain blood counts (neutrophil growth factors, platelet transfusions, RBC transfusions and erythropoietin) than did FOLFOX.

Robert De Jager of Poinard Pharmaceuticals and his study team concluded,

Neurotoxicity with FOLPI was less frequent and less severe compared to FOLFOX. Hematologic toxicity with FOLPI was manageable. FOLPI treatment of 1st line CRC had similar disease control and survival rates to FOLFOX supporting picoplatin as a potential neuropathy-sparing alternative to the use of oxaliplatin.

SOURCE: De Jager et al., Abstract B49: FOLPI (picoplatin/5-fluorouracil/leucovorin) versus modified FOLFOX-6 as a neuropathy-sparing first-line therapy for colorectal cancer, AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference 2009.

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