A phase 1 and pharmacokinetic study of gemcitabine and oxaliplatin in patients with solid tumors
Tuesday, December 6th, 2005.
Cancer Chemotherapy and Pharmacology. 2005 Nov 19;:1-8 [Epub ahead of print]. [Link].
Hui K. Gan1, Paul L. Mitchell1, Peter Galettis2, Ian D. Davis1, Jonathan Cebon1, Paul de Souza2 and Matthew Links2
(1) Department of Medical Oncology and Ludwig Institute for Cancer Research, Austin Hospital, Level D, 3KZ Building, Studley Road, Heidelberg, Melbourne, VIC, Australia
(2) Department of Medical Oncology, St George Hospital and University of New South Wales, Gray Street, 2217 Kogarah, NSW, Australia
Abstract
Purpose: This dose escalation study aimed to determine the recommended doses, toxicity and pharmacokinetics of oxaliplatin and gemcitabine given on days 1 and 8 every 21 days. This schedule may maximize dose intensity of both drugs with acceptable or reduced toxicity.
Patient and methods: Eligible patients had solid malignancies, no more than two prior courses of chemotherapy, ECOG performance status 0–2, neurotoxicity ≤ NCI-CTC grade 1 and adequate organ function. Dose escalation commenced at oxaliplatin 40 mg/m2 and gemcitabine 750 mg/m2, both given on days 1 and 8 every 21 days, and reached oxaliplatin 80 mg/m2 and gemcitabine 1,500 mg/m2. The two highest dose levels were each expanded to six patients to gain additional toxicity data.
Results: There were no dose limiting toxicities related to treatment and an MTD was not reached. Five patients (24%) had grade 3 neutropenia, without associated infection, and seven patients (33%) had grade 3/4 thrombocytopenia. Neurotoxicity was mild and no worse than grade 1. Two patients with mesothelioma (10%) had partial responses and 11 patients (52%) had disease stabilization. No pharmacokinetic interaction between oxaliplatin and gemcitabine was detected. Dose intensity was maximal at level 4 (oxaliplatin 70 mg/m2 and gemcitabine 1,250 mg/m2).
Conclusions: This schedule allows oxaliplatin and gemcitabine to be delivered at the full dose intensity of each drug with excellent tolerability and predictable pharmacokinetics. The recommended doses for phase II studies are oxaliplatin 70 mg/m2 and gemcitabine 1,250 mg/m2 on days 1 and 8 every 21 days.
Keywords: Gemcitabine - Oxaliplatin - Phase 1 - Neurotoxicity - Pharmacokinetics - Mesothelioma
Glossary
- thrombocytopenia
- (throm-bo-sigh-toe-PEEN-ee-ah) a decrease in the number of platelets in the blood; can be a side effect of chemotherapy.
- oncology
- (on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.
- grade
- The grade of a cancer reflects how abnormal it looks under the microscope. There are several grading systems for cancer, such as the Gleason score for prostate cancer. Each grading system divides cancer into those with the greatest abnormality (poorly differentiated), the least abnormality (well-differentiated), and those in between (moderately differentiated). Grading is done by the pathologist who examines the tissue from the biopsy. It is important because higher grade cancers tend to grow and spread more quickly and have a worse prognosis.
- chemotherapy
- (key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.
- cancer
- malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
