Patupilone
Patupilone (Novartis’ EPO-906), an intravenously administered formulation of epothilone B, is in Phase II trials for CaP in the United States. It is also in Phase II trials for non-small-cell lung cancer, ovarian cancer, and renal cancer.
A microtubule stabilizer, patupilone is not a substrate for the multidrug-resistance protein Pgp. The compound has demonstrated preclinical activity in taxane-sensitive and taxane-resistant tumors.
At ASCO 2004, investigators presented findings of a Phase Ha trial involving 37 patients with hormone-refractory CaP with or without metastases and with PSA higher than 20 ng / mL. The patients received 2.5 mg patupilone weekly for three weeks followed by one week of rest for up to six cycles (with a median of three). Twenty-nine patients had received prior chemotherapy. Twenty-two percent of patients had a partial PSA response, 16% had stable disease, and 43% progressed. Four of 20 patients with measurable disease had a partial response. The most common adverse events were gastrointestinal: grade three or four diarrhea, fatigue, dehydration, abdominal pain, and vomiting were reported in 19%, 14%, 8%, 5%, and 5% of patients, respectively. Grade 2 diarrhea was reported in 19% of patients. Grade 1 or 2 peripheral neuropathy occurred in 14% and 5% of patients, respectively. Grade 2 anemia occurred in 19% of patients; no other myelosuppression was reported.
Patupilone’s principal shortcoming is dose-limiting diarrhea. Neurotoxicity and myelosuppression are uncommon with this compound, unlike with ixabepilone.