PATUPILONE

EPO906

Inducing cell death through microtubule stabilization

Interference with microtubule formation and function, which is required for cell division and also endothelial-cell function, is an established antitumor strategy where agents stabilize and promote the formation of microtubules, which causes cell-cycle arrest and ultimately tumor-cell death. However, current agents such as taxanes (including paclitaxel and docetaxel) are associated with toxicities that are often treatment- and schedule-limiting, and have limited utility in treating multidrug-resistant tumor cells.¹

Patupilone (EPO906) belongs to a new class of microtubule stabilizers, the epothilones, which may have potential advantages over other microtubule stabilizers.² Preclinical studies have shown that Patupilone is more potent than paclitaxel in cell lines; is a poor/nonsubstrate for the major drug efflux pumps; and is active in taxane-resistant tumors, such as brain tumors.^1,3

Preliminary clinical data suggest a low incidence of neutropenia and alopecia, as well as predictable and generally manageable diarrhea. Clinical activity has been seen in multiple solid tumors, such as ovarian, colorectal cancer (CRC), and NSCLC- including patients with brain metastases; prostate, breast, gastric, and renal cancers; melanoma; and carcinoid tumors.^2,4,5

Patupilone is now being investigated in Phase III clinical trials in ovarian cancer, and in Phase II trials in various tumor types.

All compounds are either investigational or studied in new indications. Efficacy and safety have not been established. There is no guarantee that they will become commercially available.

1. Hofstetter B, Vuong V, Broggini-Tenzer A, et al. Patupilone acts as radiosensitizing agent in multidrug-resistant cancer cells in vitro and in vivo. Clin Cancer Res. 2005;11:1588-1596.
2. Smit WM, Sufliarsky J, Spanik S, et al. Phase I/II dose-escalation trial of patupilone every 3 weeks in patients with resistant/refractory ovarian cancer. Presented at: 13th Annual European Cancer Conference. October 30-November 3, 2005; Paris, France. Poster 909.
3. Altmann K-H, Wartmann M, O’Reilly T. Epothilones and related structures-a new class of microtubule inhibitors with potent in vivo antitumor activity. Biochim Biophys Acta. 2000;1470:M79-M91.
4. Sanchez JM, Osterland K, Perry M, et al. Phase I/II dose-escalation trial of patupilone every 3 weeks in patients with non-small cell lung cancer. Presented at: 13th Annual European Cancer Conference. October 30-November 3, 2005; Paris, France. Poster 1133.
5. Rubin EH, Rothermel J, Tesfaye F, et al. Phase I dose-finding study of weekly single-agent patupilone in patients with advanced solid tumors. J Clin Oncol. 2005;23:9120-9129.