Even colorectal cancer patients whose tumors had grown and spread after two or more other chemotherapy regimens benefitted when perifosine was added to Xeloda chemotherapy.
Both the time until cancer got worse and survival time improved with perifosine compared to a placebo. This held true for patients who had received 5-FU previously.
Based on the results of this Phase II trial, reported at ASCO 2010, a Phase III trial is underway and is recruiting colorectal cancer patients whose cancer has progressed on all standard treatments.
For the 35 patients whose results were analyzed:
- Median time to progression was 28 weeks for patients who got Xeloda plus perifosine and 11 weeks for those who got Xeloda with a placebo.
- Overall survival time was 18 months with perifosine and 11 months with Xeloda alone.
- Tumors shrank (complete or partial response) for 4 patients in the perifosine arm compared to 1 patient getting Xeloda and a placebo.
- 55 percent of patients on perifosine had stable disease that lasted more than 12 weeks compared to 33 percent for Xeloda alone.
- Overall 3 out of 4 (75 percent) had either a response to the combination of perifosine and Xeloda or stable disease, compared to 40 percent of those who got a placebo with Xeloda.
- The patient with a complete response lived 3 years before cancer got worse. The three patients with partial responses lived 21, 19, and 11 months before progression.
For 25 patients who had taken 5-FU previously:
- There was 1 partial response that lasted 19 months in the perifosine arm.
- Median overall survival time on perifosine was 15.1 months compared to 6.6 months on Xeloda only.
- Median time to progression was 18 weeks with perifosine compared to 10 weeks on Xeloda with a placebo.
Serious side effects seen more often with the perifosine-Xeloda combination were hand-foot syndrome and anemia. Less serious (grade 1 and 2) side effects that were seen more often in the combination treatment were diarrhea, fatigue, nausea, muscle pain, mouth sores, lack of appetite, hand-foot syndrome and anemia. However, patients in combination arm received treatment for a longer period of time.
Patients in the trial had cancer get worse (progress) on at least 2 previous treatments. 90 percent had been on FOLFIRI, 75 to 80 percent on FOLFOX. 3 out of 4 had received Avastin and about half Erbitux or Vectibix.
Donald Richards, MD and his colleagues reported at ASCO:
Perifosine-capecitabine (P-CAP) is a well-tolerated regimen that has promising activity over capecitabine (CAP) as 2nd or 3rd line therapy for pts with metastatic colorectal cancer. This improvement is consistent for the subset of patients with 5-FU refractory disease. A randomized phase III trial of P-CAP vs. CAP is planned for refractory colorectal cancer patients.
A larger Phase III trial is underway to confirm the results of the study. To be eligible for the X-PECT trial:
- Patient tumors must have progressed on all available standard therapies for advanced colorectal cancer including advanced colorectal cancer, including 5-FU, irinotecan, oxaliplatin, bevacizumab and for K-ras wild-type patients, Erbitux or Vectibix.
- Patients who stopped oxaliplatin before progression because of side effects are eligible.
- No previous treatment with Xeloda for metastatic colorectal cancer is allowed except as part of chemoradiation.
- Patients must have at least one tumor that can be measured with radiology scans.
Patients with dipyrimidine dehydrogenase (DPD) deficiency or previous severe reaction to 5-FU cannot enroll.
The X-PECT is being led by Dr. Johanna Bendell from the Sarah Cannon Research Institute in Nashville, TN, but there are trial sites throughout the United States.
For more information about the trial contact Keryx /AOI Pharmaceuticals at 212-531-5965.
SOURCE: Richards et al., ASCO 2010 Abstracts: Abstract #3531- Final results of a randomized phase II study of perifosine in combination with capecitabine (P-CAP) versus placebo plus capecitabine (CAP) in patients with second- or third-line metastatic colorectal cancer.