Trimetrexate and cyclophosphamide for metastatic inoperable nonsmall cell lung cancer.

Abstract

To determine the maximum tolerated dose (MTD) of trimetrexate glucuronate in combination with cyclophosphamide in patients with metastatic or inoperable nonsmall cell lung cancer (NSCLC), trimetrexate in dosages ranging from 3 to 13.5 mg/m2/day was administered intravenously (IV) to 27 patients for 5 days in combination with cyclophosphamide, 600 mg/m2, on day 1. Patients received between one and six courses of treatment at 3 week intervals, 69 treatment courses in all. Hematological toxicity was mainly mild anemia (81%), leukopenia (67%), and thrombocytopenia (52%). Nonhematological toxicity included nausea and vomiting (67%), mucositis (30%), and urticaria or rash (22%). The incidences of leukopenia and mucositis were dose related. The MTD of trimetrexate in combination with cyclophosphamide was 7.5 mg/m2/day. The dosage chosen for the Phase 2 study, based only on the hematological dose limiting toxicity, was 10.5 mg/m2/day. Of 31 patients with previously untreated metastatic or inoperable NSCLC who have entered in the Phase 2 study, 22 are evaluable for clinical efficacy (World Health Organization criteria, 1979). Treatment was discontinued in four patients because of toxicity. One patient refused further therapy. Four patients are too early to evaluate. Five patients had confirmed partial responses (23%), 12 patients achieved stable disease (54%), and five patients had progressive disease. Results suggest that trimetrexate 10.5 mg/m2/day in combination with cyclophosphamide is active against previously untreated NSCLC. Dose limiting toxicity was mucositis and myelosuppression. An 11 item linear analogue scale assessing quality of life during treatment indicated this combination was well accepted by patients and did not compromise quality of life. The Phase 2 study is continuing.

• Authors: K Mattson, P Maasilta, L Tammilehto, L R Holsti, W Grove
• Journal: Seminars in oncology (Semin Oncol) Vol. 15 Issue 2 Suppl 2 Pg. 32-7 (Apr 1988) ISSN: 0093-7754 [Print] United States
• PMID: 2835817 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Quinazolines
• Cyclophosphamide
• Trimetrexate

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Cyclophosphamide (administration & dosage)
• Drug Evaluation
• Female
• Humans
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Neoplasm Metastasis
• Quinazolines (administration & dosage)
• Trimetrexate