A phase I clinical and pharmacokinetic study of Ro 31-7453 given as a 7- or 14-day oral twice daily schedule every 4 weeks in patients with solid tumors

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Ramon SalazarJim Cassidy

Abstract

This is a dose-finding Phase I study of oral Ro 31-7453, a new class of antimitotic drug with promising preclinical activity in several chemoresistant models. Two schedules of oral Ro 31-7453 (every 12 h) given for either 7 or 14 consecutive days repeated every 4 weeks were explored consecutively. Thirty-seven patients with refractory cancer entered the study (14 on the 7-day schedule and 23 on the 14-day schedule). Median age was 63 years (range, 40-77 years), and median Karnofsky performance status was 80 (range, 60-100); the most frequent diagnosis was colorectal carcinoma (16 patients). Dose levels of 100, 200, 240, and 280 mg/m(2) twice daily (bid) for 7 days and 70, 100, 125, and 150 mg/m(2) bid for 14 days were explored. A total of 110 cycles were administered, the median number of cycles received was 3 (range, 1-7); six patients completed 6 or more cycles. Myelosuppression and mucositis were dose-limiting with both schedules. Fatigue and gastrointestinal toxicities other than mucositis were frequent but generally mild. The maximum tolerated doses were 200 mg/m(2) bid and 125 mg/m(2) bid for the 7- and 14-day schedules, respectively. Pharmacokinetic analysis showed rapid absorption and metabolism. The area under the conc...Continue Reading

References

Nov 1, 1984·European Journal of Cancer & Clinical Oncology·R RahmaniJ Barbet
Jan 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·G LiuE Warner
Aug 6, 1997·Journal of the National Cancer Institute·R SimonM C Christian

❮ Previous
Next ❯

Citations

Feb 18, 2003·Journal of Internal Medicine·P Nygren, R Larsson
Mar 28, 2008·Expert Opinion on Investigational Drugs·Michelle Harrison, Charles Swanton
Jun 21, 2008·Molecular Cancer Therapeutics·Theresa M LaValleeAnthony M Treston

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.