A. T. van Oosterom

INHIBITION OF OSTEOLYTIC BONE LESIONS BY (3-AMINO-1-HYDROXYPROPYLIDENE)-1, 1-BISPHOSPHONATE (A.P.D.)

14 patients with osteolytic bone disease due to breast cancer or myeloma, 7 of whom had hypercalcaemia, received oral treatment with (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (A.P.D.). Serum-calcium dropped to low normal values in all 14 patients, accompanied by a decrease in urine calcium and hydroxyproline excretion-rate. The results show that A.P.D. may inhibit tumour-induced osteolysis.

Combination chemotherapy with cis-diammine-dichloro-platinum, vinblastine, and bleomycin in advanced testicular non-seminoma

40 patients with disseminated testicular non-seminoma were treated with cis-diammine-dichloro-platinum, vinblastine, and bleomycin. Complete remission was achieved in 24 (60%) patients and partial remission in 11 (28%). 22 of the 24 complete responders, who have been followed-up for a median of 11 months, have been tumour-free for 5--30 months. There were 3 drug-related deaths. This regimen is the most effective remission-induction treatment available for disseminated testicular non-seminoma. Patients should be treated in centres experienced in the specialised management of this potentia-ly curable disease.

Determination of the underivatized antineoplastic drugs cyclophosphamide and 5-fluorouracil and some of their metabolites by capillary gas chromatography combined with electron-capture and nitrogen-phosphorus selective detection.

A rapid and sensitive method for the determination of cyclophosphamide (CP) and 5-fluorouracil (5-FU) and some of their metabolites in one analysis has been developed. Surface-coated open-tubular OV-275 columns were combined with electron-capture detection and nitrogen-phosphorus selective detection. The influence of the column diameter on the separation is shown. Extraction with 2-propanol-diethyl ether (22:77) allows the isolation of CP, 5-FU and their analogues in one extraction step. The assay was applied to some pharmacokinetic experiments with chemotherapeutically treated patients and with a WAG/Rij rat.

Combination chemotherapy with cisplatin and VM-26 in advanced transitional cell carcinoma of the bladder☆

Abstract Forty-one evaluable patients with bidimensionally measurable metastases of transitional cell carcinoma of the bladder were treated with cisplatin 70 mg/m 2 i.v. on day 1 and VM-26 100 mg/m 2 i.v. on days 1 and 2, every 3 weeks . Response was evaluated after 2 treatment cycles. Complete response (CR) was achieved in 4 patients (10%) and partial response (PR) in 17 (41%). The median response duration was 6 months . In this group of previously untreated patients the combination of cisplatin and VM-26 did not appear to yield better response rates than would be expected from cisplain alone.

Current status of systemic chemotherapy in the treatment of advanced ovarian cancer with emphasis on CHAP-5

In patients with advanced ovarian cancer, initial treatment with combination chemotherapy, including cyclophosphamide and cis-platinum diamminedichloride (cis-platinum), produces response and progression-free survival results which are superior to those achieved with alkylating single-agent chemotherapy. Unfortunately most schedules have not resulted in a statistically significant improvement of overall survival. So far one of the most effective combination regimens is the four-drug regimen CHAP-5 that consists of cyclophosphamide, hexamethylmelamine, adriamycin, and cis-platinum. This regimen is the first schedule to result in significant improved survival times compared with a second combination schedule, i.e. Hexa-CAF, which is at least as good as alkylating therapy alone. The CHAP-5 regimen was rather toxic but it was manageable and easy to apply in daily practice. Further improvement of the treatment results in advanced ovarian carcinoma will be difficult because no effective new drugs are available. In future clinical research it must be tried to decrease the toxicity and morbidity of the current schedules without reducing efficacy and survival.

Combination Chemotherapy with or without hexamethylmelamine in alkylating agent-resistant ovarian carcinoma

The study was designed to determine the efficacy of a two‐drug and three‐drug combination chemotherapy regimen for patients with advanced epithelial ovarian carcinoma resistant to alkylating monotherapy. Patients were randomized to receive either Adriamycin (doxorubicin) and cis‐diamminedichloroplatinum(II) (AP) repeated every 3 weeks, or AP plus hexamethylmelamine (HAP) repeated every 5 weeks. Forty‐five patients were evaluable for response and 49 for survival. No significant differences were found between the treatment groups as to response rate, progression‐free survival, and survival. A remission was achieved in 20% of the patients and stable disease in another 20%. Median progression‐free survival of all patients was only 4 months (median survival, 6 months). All patients showed progressive disease within 13 months after the onset of chemotherapy. Patients responding to treatment and those with an interval of more than 2 years between the initial diagnosis and cancer recurrence, experienced prolonged survival. Two conclusions can be drawn from the results of this study; neither of the regimens is superior to the other, and the effect of both in alkylator‐resistant patients with ovarian cancer are meager. In studies on salvage chemotherapy, to the contrary, these combinations induced remissions in more than 40% of the patients. This difference in response rate might be due to differences between the prognostic factors of the patient populations. Better results are to be expected when these drugs are used in initial drug programs for previously untreated patients.

Predictive testing in cancer chemotherapy

Severalin vivo methods have been assessed for their capacity to predict sensitivity for anticancer agents in humans. Standard strategies have been developed for screening purposes. Adjustments of these strategies are frequently suggested in reports in which the correlation between assay results and clinical therapeutic efficacy is analysed. Low predictivity and high costs of these assays are important reasons for changing the screening strategy.In vivo methods which predict the clinical response in the individual patient, are under investigation. Only the results of the subrenal capsule assay (in normal mice) have been correlated with the clinical response in a larger study. The criticism of the method and the low predictivity for sensitivity in a prospective study provide no reason for optimism. Methods which study changes predicting the clinical response in patients are still in a developmental phase.