Part 2:
MLN2704 in patients with advanced androgen independent metastatic prostate
cancer; updated results
A single ascending dose phase I study of MLN2704, led by Howard I. Scher,
M.D. at Memorial Sloan-Kettering, New York and Mario Eisenberger, M.D. at
Johns Hopkins Oncology Center, Maryland enrolled 23 patients and examined the
maximum tolerated dose, dose-limiting toxicity, pharmacokinetics and
immunogenicity of MLN2704. Patients received MLN2704 at doses ranging from 18
to 343mg/m2. Responses in patients with measurable disease were evaluated
based on the RECIST (Response Evaluation Criteria In Solid Tumors) criteria
and confirmed four to six weeks after the first documentation of a complete or
partial response. In addition, anti-tumor activity was evaluated based on a
sustained PSA decline of at least 50 percent confirmed by two separate
measurements at least four weeks apart. Dose escalation continued if no dose-
limiting toxicity was observed. Investigators reported the following results:
* Of 11 patients with measurable disease, one patient treated with a
264mg/m2 dose, achieved a durable partial response, including a PSA
decline of more than 50 percent . This patient received 14 doses prior
to measurable disease progression at 47 weeks;
* One additional patient, treated with a 343mg/m2 dose, achieved a PSA
decline of more than 50 percent that persisted for 24 weeks;
* Four patients achieved stable disease;
* Toxicities greater than grade three occurred in three patients
including an episode of uncomplicated febrile neutropenia with
lymphopenia and leukopenia, lymphopenia, and a transient grade three
elevation in hepatic transaminases. No grade four toxicities were
observed; and
* No immunogenicity was observed despite repeat dosing. |
