Promising Results Combining Alimta?with Other Agents in Advanced Colorectal Cancer

Based on the single agent activity of Alimta? Eloxatin? and Camptosar?in the treatment of locally advanced or metastatic colorectal cancer (CRC), investigators are now evaluating combinatio of these drugs. According to a presentation at the Chemotherapy Foundation Symposium XXI, one study combining Alimta?and Eloxatin?has already suggested efficacy as first-line treatment and further studies are ongoing.

Two multi-center, phase II trials (one U.S. 1, one Canadian 2) evaluated Alimta?(600 mg/m2) as a single agent in patients with locally advanced or metastatic CRC. The Canadian study was done in 32 previously untreated patients while the US study involved 46 patients and allowed those who had received adjuvant treatment, provided that treatment was completed one year prior to enrollment. Overall re o e rates were similar, 17.2% in the Canadian trial, 15.4% in the US trial, as were median time to progre ion, 3.3 months and 4.4 months, re ectively. In the U.S. trial, the medial survival was 16.2 months and 65% of the patients were alive at one year.

At the time that these studies were conducted, the hematologic toxicities characteristic of Alimta?were still being addre ed, hence su tantial adverse effects were o erved and dose reductio were required. Su equently, several studies in various tumor types have shown this toxicity to be ameliorated through su lementation with low dose folic acid and vitamin B12, and this is now an accepted part of any Alimta?protocol.

Camptosar?was combined with Alimta?in a phase II study 3 to determine the maximum tolerated doses (MTD) of the two drugs together as second-line therapy for advanced CRC. With 12 patients enrolled at three dose levels, the MTD was reached at 500 mg/m2 for Alimta?and 350 mg/m2 for Camptosar?but only one partial re o e and seven patients with stable disease were recorded. A phase II A trial 4 combined Alimta?(500 mg/m2) with Eloxatin?(120 mg/m2) every three weeks for six cycles as first-line treatment. Of the 47 patients evaluable for re o e, one complete re o e and 14 partial re o es were o erved for an overall re o e rate of 28% and a median duration of re o e of 5.7 months. Most notable was the minimal toxicity o erved with this regimen relative to FOLFOX (5-FU/Eloxatin? or FOLFIRI (5-FU with folinic acid).

Studies currently accruing patients include an Alimta?plus Eloxatin?protocol, which will look at a more dose inte e regimen as it is administered every two weeks. Another trial will compare Alimta?plus Eloxatin?to FOLFOX4 as frontline therapy and yet another will compare Alimta?plus Camptosar?to FOLFIRI. The latter is designed to also measure metabolic enzymes to determine if there is a biochemical or genomic profile that may identity patients more susceptible to the activity of Alimta?relative to 5-FU.

References

1. John W, Picus J, Blancke CD

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