PHIC [NSC-350602; (1,2-diaminocyclohexane) (isocitrato) platinum (II)] is a new highly water-soluble platinum derivative. Preclinical studies showed antitumor activity on a wide range of tumors, no cross-resistance with cisplatin and little or no nephrotoxicity in mice and baboons. A phase I clinical trial was then initiated at doses of 300 mg/m2 infused intravenously over one hour without induced diuresis or hydration. Dosages were escalated up to 1500 mg/m2. A total of 29 patients received 52 courses of treatment. The most important side-effect is thrombocytopenia which is rapidly reversible. Nausea and/or vomiting were mild or moderate with onset 1 hr after the end of the infusion and seldom persisted beyond 24 hrs. Measurements of biological parameters did not reveal significant evidence of nephrotoxicity except in one patient who developed urinary tract infection and for whom hemodialysis became necessary. No change in the audiogram could be demonstrated. Peripheral neuropathy was documented in one patient, and in two other patients to whom morphine was given confusional episodes were observed. Although no antitumor effect was observed, there was apparent stabilization of disease. Pharmacokinetic parameters were calculated in twelve out of these 29 patients. Based upon total platinum plasma concentrations, the elimination half-life is 58.3 hrs and the plasma clearance is 21.2 ml/min with an apparent volume of distribution of 7.6 liters. However, considering both plasma concentrations and urinary excretion, we could estimate the half-life of free filterable species (60 min), the plasma clearance (125 ml/min) and the renal clearance (86 ml/min). Mean urinary excretion is 64.4% of the dose after 6 days and 53.1% at 24 hrs. Other administration protocols are suggested, based upon these pharmacokinetic parameters.

Forty patients with advanced renal cell carcinoma were treated with elliptinium by a weekly infusion of 100 mg/m2. Of 38 evaluable patients, five had an objective response (13.2%). Average response duration was 8 months (range, 5-11). The major dose-limiting toxic effect was induction of antielliptinium antibodies, with the risk of intravascular hemolysis. Elliptinium has modest activity in advanced renal cell cancer and does not produce myelosuppression.

Polyadenylic-polyuridylic acid [poly(A) X poly(U)], an immunomodulator, has been shown to have antitumor effects in rodents and in a randomized clinical trial as an adjuvant to surgery in patients with operable breast cancer. The purpose of the present study was to determine the following: (a) clinical tolerance and safety of poly(A) X poly(U) in 13 patients with advanced cancer receiving a single dose of this duplex, using increasing amounts per intravenous injection of 90, 180, 300, and 450 mg; (b) if such high doses increased the level of interferon-mediated protein kinase and enhanced natural killer (NK) cell activity as observed previously with lower doses; and (c) if circulating interferon could be detected. No toxicity was observed in the 13 patients by close observation of clinical parameters, hemogram, and renal and liver functions. Increases of interferon-mediated protein kinase and of NK cell activity were observed, but there was no correlation between the magnitude of the responses and the dose of poly(A) X poly(U). No circulating interferon was detected. We conclude that poly(A) X poly(U) is not toxic in humans, at least up to a dose of 450 mg.

The results obtained with N-methyl-hydroxy-elliptinium acetate (NMHE) in the treatment of 22 assessable adult patients with metastatic renal cancer are reported. According to the WHO criteria, there were 10 responses, including 7 stabilizations, 2 partial remissions (greater than 50%) and one complete and durable remission. Since there is no other effective medical treatment for this type of tumour, and since the protocol used so far appears to have low toxicity and makes it possible to evaluate the value of the drug within 4 to 6 weeks, the trial will be extended in order to determine more precisely (+/- 5%) the degree of effectiveness of NMHE.

The management of pulmonary metastases from osteosarcomas rests at present on thoracic surgery combined with chemotherapy. Until the beginning of the seventies chemotherapy proved very disappointing. With adriamycin, methotrexate in high doses followed by folinic acid and, more recently, platinum cis-dichlorodiamine, remissions, which are usually partial, are obtained in a significant proportion of patients (at least 30%). The addition of less active agents such as vincristine, cyclophosphamide, actinomycin D and bleomycin is helpful. Among 31 patients with pulmonary metastases from treated osteosarcomas seen at the Gustave Roussy Institute, 18 underwent thoracic surgery as the first treatment; in 10, surgery was followed by chemotherapy with adriamycin, vincristine, methotrexate in high doses + folinic acid + cyclophosphamide. Five patients are in complete remission 27, 30, 49, 50 and 77 months after the surgical procedure. 12 patients were initially treated with a similar chemotherapeutic regimen; a subsequent thoracic surgical procedure was undertaken in two patients who died 18 and 30 months after the pulmonary metastases had appeared. In one patient, the metastases were treated by irradiation. These results are compared to previous reports in the medical literature.