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Between 1957 and February 1981, 782 patients received cytotoxic chemotherapy for gestational trophoblastic tumors (GTT) in the Department of Medical Oncology, Charing Cross Hospital (London, England). Sixty‐nine (8.8%) patients had central nervous system (CNS) metastases. Thirty‐three of them (48%) presented with CNS disease prior to treatment (CNS presentation group), and 36 (52%) developed CNS disease while on treatment, or relapsed in the CNS after an initial complete or partial remission (late CNS group). Treatment included systemic and intrathecal chemotherapy, and, in several cases neurosurgery, whole brain irradiation, and immunotherapy. Life‐table analysis projects an overall survival of 49% for the CNS presentation group and 6% for the late CNS group. Prognosis has improved with time; prior to 1974, 38% of the CNS presentation group and none of the late CNS group survived. After 1974 overall survival has been 80% in the CNS presentation group and 25% in the late CNS group. The principal elements in the successful management of such cases are: (1) CNS prophylaxis with intrathecal methotrexate for patients at risk of developing brain metastases; (2) early detection of CNS lesions by prompt recognition of their clinical features, measurement of the ratio of CSF to serum human chorionic gonadotropin concentration, and appropriate use of computerized tomography of the brain; and (3) a combination of systemic and intrathecal therapy for patients developing brain secondaries.

The synthesis of three novel prodrugs, 4-[bis[2-(mesyloxy)ethyl]amino]benzoyl-L-glutamic acid (7), 4-[(2-chloroethyl)[2-(mesyloxy)ethyl]amino]benzoyl-L-glutamic acid (8), and 4-[bis(2-chloroethyl)amino]benzoyl-L-glutamic acid (9), for use as anticancer agents, is described here. Each is a bifunctional alkylating agent in which the activating effect of the ionized carboxyl function is masked through an amide bond to the glutamic acid residue. These relatively inactive prodrugs are designed to be activated to their corresponding nitrogen alkylating agents (10, 11, and 12, respectively) at a tumor site by prior administration of a monoclonal antibody conjugated to the bacterial enzyme carboxypeptidase G2 (CPG2). The viability of two different tumor cell lines was monitored with each prodrug in the presence of CPG2. All three compounds showed substantial prodrug activity--with conversion to the corresponding active drug leading to greatly increased cytotoxicity.

The prognostic value of serum CA-125 measurements was assessed in 54 patients with advanced ovarian adenocarcinoma. All patients received a minimum of two courses of carboplatin as part of the North Thames Cooperative Group trial. With a minimum follow-up of 6 months, 37 patients (69%) have clinical evidence of progressive disease and 28 have died. The absolute prechemotherapy level of CA-125 was of no value in predicting which patients would develop progressive disease. However, the change in CA-125 levels from before chemotherapy to 1 month later, after one course of carboplatin, could be used to divide patients into different prognostic groups. The best discrimination was found by dividing the patients into those who showed a greater than sevenfold decrease in CA-125 levels and those who showed a smaller change. Eight of 14 (58%) patients with a greater than sevenfold decrease in CA-125 levels remain disease-free compared with three of 36 (9%) patients with a lesser fall (P = .0005). The change in CA-125 levels during the first month of chemotherapy may indicate which patients should be offered alternative or symptomatic therapy and which should continue with the currently available toxic chemotherapy.