Related Experiment Videos
Cisplatin and dichloromethotrexate: a pharmacologically rational combination
R B Natale1, R H Wheeler, J A Roberts
1Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
NCI Monographs : a Publication of the National Cancer Institute
|January 1, 1987
Summary
Dichloromethotrexate (DCM) combined with cisplatin (CDDP) shows promise for treating head and neck, bladder, and cervical cancers. This combination therapy demonstrated significant response rates with tolerable side effects and no significant kidney damage.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Dichloromethotrexate (DCM), a methotrexate analog, is a folate antagonist metabolized by the liver.
- DCM exhibits no nephrotoxicity, and its pharmacokinetics are unaffected by renal function.
- Epithelial carcinomas of the head and neck, bladder, and cervix are known to respond to cisplatin (CDDP) and methotrexate (MTX).
Purpose of the Study:
- To investigate the feasibility of administering a maximum tolerated dose of DCM.
- To evaluate DCM in combination with high-dose cisplatin (CDDP).
- To assess efficacy and safety in patients with head and neck, bladder, or cervical cancer.
Main Methods:
- Dose-escalation study to determine the maximum tolerated dose (MTD) of DCM.
- Combination therapy administered on a weekly schedule.
- Patient cohorts included head and neck, bladder, and cervical cancer.
Main Results:
- Overall response rates were 54% (head and neck), 57% (bladder), and 50% (cervical cancer).
- Complete response rates were 25% (head and neck), 19% (bladder), and 36% (cervical cancer).
- The combination therapy was well-tolerated with no significant nephrotoxicity.
Conclusions:
- DCM can be safely administered at its MTD weekly in combination with CDDP.
- The DCM-CDDP combination shows significant efficacy in advanced epithelial carcinomas.
- This regimen offers a tolerable treatment option without compromising renal function.