Phase II studies of single-agent cimetidine and the combination N-phosphonacetyl-L-aspartate (NSC-224131) plus L-alanosine (NSC-153353) in advanced malignant melanoma.

Abstract

We conducted parallel phase II trials of cimetidine as a single agent and the combination N-phosphonacetyl-L-aspartate (PALA) plus L-alanosine among 40 previously untreated patients with biopsy-proven, measurable disseminated malignant melanoma. We did not design the trial to be a comparative assessment of the two regimens. Among 19 patients treated with cimetidine, 300 mg orally four times daily, there was one complete response of extensive pleural and pulmonary metastases for 16+ months and two partial regressions of soft tissue lesions for 7 and 21+ months, respectively. Among 21 patients treated with the combination regimen, there was only one partial response in soft tissue for 1 month. The median times to progression and death were 1.4 and 6 months, respectively, for cimetidine, and 1.3 and 4 months, respectively, from the combination of PALA plus L-alanosine. Among patients who progressed on initial treatment, there were no responses in 12 who received crossover therapy with cimetidine and 11 with the combination regimen. Two patients treated with the combination program had severe stomatitis, two developed renal failure, and one had severe leukopenia and thrombocytopenia. Recognizing the limitations of small sample size, these early observations suggest that cimetidine may have intriguing implications in the management of disseminated malignant melanoma.

• Authors: R F Morton, E T Creagan, S A Cullinan, J A Mailliard, L Ebbert, M H Veeder, M Chang
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 5 Issue 7 Pg. 1078-82 (Jul 1987) ISSN: 0732-183X [Print] United States
• PMID: 3598611 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• alanosine
• Aspartic Acid
• sparfosic acid
• Cimetidine
• Phosphonoacetic Acid
• Alanine

Topics

• Alanine (administration & dosage, analogs & derivatives)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Aspartic Acid (administration & dosage, analogs & derivatives)
• Cimetidine (therapeutic use)
• Drug Evaluation
• Female
• Humans
• Lung Neoplasms (drug therapy, secondary)
• Male
• Melanoma (drug therapy, secondary)
• Middle Aged
• Phosphonoacetic Acid (administration & dosage, analogs & derivatives)
• Pleural Neoplasms (drug therapy, secondary)
• Soft Tissue Neoplasms (drug therapy, secondary)