Phase I trial of pomalidomide given for patients with advanced solid tumors.

Abstract

PURPOSE:

To determine the safety, the maximal tolerated dose, and to assess for any clinical activity of pomalidomide given to patients with advanced solid tumors.

PATIENTS AND METHODS:

Patients with incurable solid tumors were enrolled. Two different dosing schedules were explored. In Cohort A patients were given pomalidomide once daily for 21 days followed by a 7 day rest. For Cohort B additional patients were recruited to receive pomalidomide given once daily for 28 consecutive days. Dose-limiting toxicity was defined as ≥grade 3 non-hematological toxicity that occurs during cycle 1 and that does not resolve to ≤grade 1 by day 35. Subjects must have received optimal symptomatic treatment for ≥grade 3 nausea, vomiting, or diarrhea to be considered a DLT. Grade 4 transaminitis was considered to be a DLT while grade 3 transaminitis must be present >7 days to be a DLT. Grade 3 febrile neutropenia was considered a DLT. Grade 4 neutropenia, without a fever, was a DLT if the neutropenia did not improve to ≤grade 1 by day 35 of cycle one. Platelet count ≤25,000/mm(3) must improve to ≥75,000/mm(3) by day 35 of cycle one in order not to be considered a DLT. If a patient did not complete one cycle of therapy, for reasons other than a DLT, a replacement subject was added to the same cohort level.

RESULTS:

A total of 40 patients were enrolled. In Cohort A, three patients received pomalidomide at 5 mg daily without any significant toxicity. Two patients in the 10 mg cohort experienced dose-limiting toxicities of two episodes of grade 3 dyspnea and one grade 4 neutropenia. Six patients were then enrolled at the 7 mg daily of pomalidomide, and no dose-limiting events were observed. In Cohort B, 29 patients were enrolled and the maximal tolerated dose was 4 mg once daily. Stable disease in a variety of tumors was observed.

CONCLUSIONS:

Pomalidomide was well tolerated and the recommended phase II dosing schedules are 7 mg daily given for 21 days followed by a 7-day rest or pomalidomide 4 mg given on an uninterrupted daily schedule.

• Authors: Matthew M Cooney, Charles Nock, Joseph Bokar, Smitha Krishnamurthi, Joseph Gibbons, Mary Beth Rodal, Anne Ness, Scot C Remick, Robert Dreicer, Afshin Dowlati
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 70 Issue 5 Pg. 755-61 (Nov 2012) ISSN: 1432-0843 [Electronic] Germany
• PMID: 22875080 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Immunologic Factors
• Thalidomide
• pomalidomide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Cohort Studies
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Humans
• Immunologic Factors (administration & dosage, adverse effects, therapeutic use)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy, pathology)
• Thalidomide (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Treatment Outcome
• Young Adult