Pemetrexed combined with paclitaxel: a dose-finding study evaluating three schedules in solid tumors
Friday, October 31st, 2008.
Investigational New Drugs. 2008 Oct 28. [Epub ahead of print] [Link]
Hanauske AR, Dumez H, Piccart M, Yilmaz E, Graefe T, Gil T, Simms L, Musib L, Awada A.
St. Georg Hospital, Ahrensburger Weg 129b, 22359, Hamburg, Germany, hanauskeax@lilly.com.
Abstract
The objectives of this phase I study were to determine the maximum tolerated dose (MTD), recommended phase II dose (RD), antitumor activity, safety, and pharmacokinetics of pemetrexed–paclitaxel combination. Patients (N = 95) with advanced solid tumors were assigned to three schedules (21-day cycles [q21d]). Starting doses for each schedule of pemetrexed and paclitaxel, respectively, were: (S1) 400 and 135 mg/m2 on d1; (S2) 400 mg/m2 d1 and 40 mg/m2 d1 and d8; S3) 400 mg/m2 d8 and 30 mg/m2 d1 and d8. MTD was 500/135 mg/m2 (S1), 400/40 mg/m2 (S2), and 500/120 mg/m2 (S3). Most common dose limiting toxicities were febrile neutropenia, fatigue, and neuromotor toxicities. Most common toxicity was grade 3/4 lymphopenia. Four patients had partial response, 43 patients had stable disease. The RD determined was pemetrexed 500 mg/m2 (d8) and paclitaxel 90 mg/m2 (d1 and d8), q21d. The combination was well tolerated and showed efficacy in thyroid carcinoma and mesothelioma.
Keywords: Pemetrexed – Paclitaxel – Phase I – Combination chemotherapy – Vitamin supplementation
Glossary
- 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.
- carcinoma
- (car-sin-o-ma) a malignant tumor that begins in the lining layer (epithelial cells) of organs. At least 80% of all cancers are carcinomas.
- mesothelioma
- a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.
- pemetrexed
- chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.
