[Subcutaneous administration of interleukin-2 in ambulatory treatment of patients with metastatic renal cancer. Three-year results of the SCAPP I program]. / Traitement ambulatoire par interleukine 2 administrée par voie sous-cutanée chez des patients porteurs d'un cancer du rein métastatique. Résultats à 3 ans du programme SCAPP i.

We report a french experience of subcutaneous administration of interleukin-2 in treatment of patients with metastatic renal cell carcinoma. Thirty-nine patients with metastatic renal cell carcinoma were included in the study. During the 10-week induction period, interleukin-2 was administrated subcutaneously 5 days a week for 8 weeks. The weekly dosage were 90 MIU during weeks 1 and 6; 63 MIU during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with stable disease received maintenance treatment which was discontinued upon the appearance of disease progression or unacceptable toxicity. During the maintenance period, interleukin-2 was administered 5 days a week for 4 weeks followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63 MIU in weeks 2 to 4. After completion of induction treatment, 7 of 39 evaluable patients (18%) had objective responses with 1 complete response. A diminution of dose or interruption of treatment occurred with 7 patients because severe toxicity. Other systemic side effects in the remaining patients were acceptable. Seventeen patients received maintenance treatment. The median follow-up of all the patients included was 21 months. The 1, 2 and 3 years survivals were 64%, 33% and 22% respectively. This multicentric trial confirms the efficacity of subcutaneously-administered interleukin-2 in patients with metastatic renal cell carcinoma in terms of both response rate and survival. Unfortunately, increasing total doses of administrated interleukin-2 does not seem to increase efficacity according to response rate, but is more toxic.

Subcutaneous recombinant interleukin-2 (rIL-2) in out-patients with metastatic renal cell carcinoma. Results of a multicenter SCAPP1 trial.

BACKGROUND: This multicenter phase II trial was conducted in order to evaluate the efficacy and toxicity of the subcutaneous route of administration of rIL-2 in the treatment of patients with metastatic renal cell carcinoma and to check whether an increased cumulative dose of rIL-2 increases efficacy. PATIENTS AND METHODS: Thirty-nine patients with metastatic renal cell carcinoma were included in this study. During the induction period, rIL-2 was administered subcutaneously 5 days a week for 8 weeks. The weekly dosages were 90 MIU during weeks 1 and 6;63 MIU during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with stable disease received maintenance treatment which was discontinued upon the appearance of disease progression or unacceptable toxicity. During the maintenance period, rIL-2 was administered 5 days a week for 4 weeks followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63 MIU in weeks 2 to 4. RESULTS: After completion of induction treatment, 7 of 39 evaluable patients (18%) had objective responses (95% CI: 9% to 37%) with one complete response. Treatment was interrupted or reduced due to toxicity for seven patients: Neuropsychiatric symptoms (3 patients), joint pain (1 patient), major asthenia and anorexia (1 patient), stroke (1 patient), and septicemia (1 patient). Other systemic side effects in the remaining patients were acceptable. Seventeen patients received maintenance treatment. In none of the patients did the response status improve during this maintenance period. The median follow-up of all of the patients included was 19 months. The one- and two-year survivals were 65% and 33%, respectively, ad the median duration of response was 11 months (5 to 16+). CONCLUSIONS: This multicentric study confirms the efficacy of subcutaneously-administered rIL-2 in patients with metastatic renal cell carcinoma in terms of both response rate and survival. The role of a maintenance therapy needs further evaluation.

Phase I-II constant infusion of adriamycin (doxorubicin) by ambulatory pump delivery system in heavily pretreated (including adriamycin) breast cancer patients.

Previous studies have shown that the protracted infusion of adriamycin (ADM) by the ambulatory delivery system can significantly decrease both the cardiac and hematological toxicity caused by intermittent bolus administration. We treated 27 patients with metastatic breast cancer who had been heavily pretreated with regimens including ADM. Treatment consisted of 15- or 25-day courses of ADM at a mean dose of 3.8 mg/m2 (2.2-4.5 mg/m2) infused by programmable portable pump. Early cardiac toxicity was detected by echocardiography-Doppler. Two-dimensional echocardiography made possible the detection of interventricular septum hypokinetics, an early sign of a decrease of systolic function of the left ventricle. Despite the very high cumulative dose of ADM (mean dose 777.79 mg/m2, range 282-1647 mg/m2) received by these patients, no clinical heart failure was observed. Most frequently observed complications were oral mucositis, Grade 2 and 3 (10 patients), and complications related to the drug delivery system (15/137 courses). Hematological toxicity was minimal. Seven Grade 2 and five Grade 3 (but no Grade 4) alopecia were observed. Objective response was obtained in four of 24 patients (17%) evaluated for response, (only 21 were fully evaluable): one complete response and three partial responses (duration: 6.6, 7 and 11 months, respectively). Stabilization was seen in 14 patients lasting three to 26 months. The performance status and symptoms of nine of the patients (37%) was significantly improved. Our results show that continuous infusion of ADM is well tolerated and provides palliation to patients with metastatic breast cancer. It merits a trial as first-line treatment.

A phase I trial of trans-1-diaminocyclohexane oxalato-platinum (l-OHP).

Oxalato-platinum in a new platinum derivative which was found to be active in experimental tumors and devoid of nephrotoxicity. A phase I study was conducted in cancer patients according to a new design following the recommendations of our Institution's ethical committee to avoid the major drawback of classical phase I studies in which many patients receive the experimental drug at doses far under the potentially active dose extrapolated from experimental studies. The potentially active dose of l-OHP was determined from the Maximally Efficient Dose Range (MEDR) to be between 45 mg/m2 (subcurative dose) and 67 mg/m2 (subtoxic dose). The patients in this study received with increasing intervals 1/100, 1/10, 1/5, 1/3, 1/2, 2/3, 3/4, 1, of the low dose of the MEDR, this dose being reached after 90 to 120 days on study. 23 evaluable patients have entered the trial of which 19 reached the low dose of MEDR (45 mg/m2). Gastro-intestinal toxicity, nausea and vomiting, similar to those with CDDP occurred in all patients at or above the dose of 30 mg/m2. Renal toxicity was monitored with creatinine level and did not occur in any patient at any dose nor did significant hematologic toxicity occur. Thus nausea and vomiting appear to be the limiting toxicity of the drug. Responses were observed in this phase I study in lung cancer (1), breast cancer (1), melanoma (1) and perhaps hepatoma (major decrease in alpha FP levels) (1). The proposed starting dose for phase II studies is 45 mg/m2 but we plan to continue dose escalation during the phase II according to the design of Jones and Holland. This new study design allows each patient entering a phase I study to be treated with a potentially active dose of the drug studied.