Trimetrexate glucuronate associated with anti-Kaposi sarcoma effect

Trimetrexate glucuronate, a dihydrofolate reductase inhibitor related to methotrexate, was developed by Parke-Davis as an alternative antineoplastic agent for tumors, especially sarcomas, that had developed resistance to methotrexate. This is a report on a patient with AIDS who developed Pneumocystis carinii pneumonia, which was treated with trimethoprim sulfamethoxazole (Bactrim) with poor response, then with pentamidine with poor response, and finally with trimetrexate glucuronate (Neutrexin) and leucovorin rescue, with good response. The patient also suffered from cutaneous and visceral Kaposi's sarcoma (KS), which had been treated with high- dose HCG1 and well recognized chemotherapeutic protocols. Both HCG and chemotherapy resulted in tumor regression. The patient's KS flared, however, when he developed pneumocystis pneumonia. When trimetrexate glucuronate and leucovorin rescue were administered, his tumor burden decreased significantly, suggesting that trimetrexate glucuronate may have some activity against KS. The regression of KS in this anecdotal observation may be secondary to a delayed response from HCG and/or chemotherapy, or secondary to a spontaneous partial regression. Such regression may only be of the decreased edema around the KS lesions and not the neoplastic tissue itself. If other clinicians see this same phenomenon, however, it is possible that trimetrexate glucuronate may have an anti-KS effect. Such future clinical observations would warrant further testing at the basic science level.