A method for the assay of 1,3,3,5,5-pentakis-(azaridino)-lambda 6,2,4,6,3 lambda 5,5 lambda 5-thiatriazadiphosphorine-1-oxide (SOAz), a new anticancer drug of which the clinical trials are in progress, is described. This method is based on capillary gas chromatography using a thermionic detector. The lower detection limit was 100 pg per injection and a coefficient of variation smaller than 5% could be obtained when parathion was used as external standard. The method is suitable for biological samples and therefore has been proposed for clinical pharmacokinetic studies as well as for the determination of patterns of SOAz distribution in several organs of the mouse. A preliminary clinical study showed that the serum decay curves of SOAz could be fitted to an open two-compartment model for drug disappearance.

Adenocarcinoma↗

PubMed1983

An EORTC phase II study of vindesine in advanced prostate cancer.

In a phase II study of vindesine in patients with bi-dimensionally measurable primary or metastatic prostate cancer, 27 patients (given 3 mg/m2 weekly for at least 4 treatment cycles) were evaluable for response 6 weeks from the start of treatment. Dose escalation to 4 mg/m2 weekly was attempted. Five patients (19%) achieved a partial remission of short duration, 11 patients (41%) showed no change and 11 patients (41%) showed progression. Thirty-one patients were evaluable for toxicity. Neurotoxicity occurred in 58% (severe in 23%) and was apparently cumulative dose-dependent, although there was variable individual sensitivity. Haematological toxicity was evidenced by lack of dose escalation in 32% of patients, dose delay in 71% and some degree of anaemia in 48%. Alopecia occurred in 55%. Other toxicities were few and minor. Vindesine shows marginal activity in prostatic cancer but at this dose schedule causes appreciable toxicity.

Aged↗

PubMed1983

Accumulation of non-cycling cells with a G2-DNA content in ageing solid tumours. Study of the Ca 755 mammary adenocarcinoma of mice.

Mouse mammary adenocarcinoma Ca 755 was studied at two times in its growth: the exponential (8 days) and plateau phase (20 days). Cycling cells were labelled with [3H]thymidine injections at 4-hr intervals over 72-hr periods, i.e. three to five times longer than the generation times for the twentieth day and eighth day tumour cells respectively. By autoradiography, the increase of non-cycling cells in ageing tumours was confirmed. By single cell cytophotometry used after Feulgen staining it has been shown that the cells with a high DNA content (especially a G2-DNA amount) were in a higher proportion in the twentieth day tumours than in their eighth day counterparts. Combined cytophotometric and autoradiographic procedures have shown that nearly all cells with a G2-DNA content entered a non-cycling state in ageing tumours.

Adenocarcinoma↗

PubMed1982

Phase I study of SOAz.

SOAz, an inorganic cyclic derivative, was given as a single iv injection through one cycle in a phase I trial. Dose-limiting toxic effects noted were neutropenia and thrombocytopenia occurring at doses greater than or equal to 220 mg/M2 in patients with prior myelosuppressive treatment. The time to nadir for blood cell counts was long, as well as the time to recovery, so cumulative toxicity could be suspected. No other significant toxicity was noted. In patients with measurable volume, no significant antitumor responses were seen. For further study, the dose of 220 mg/m2 every 6-8 weeks according to hematologic restoration is recommended.

Adult↗

PubMed1981

Thioproline toxicity.

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Carcinoma, Squamous Cell↗

PubMed1979

[Meningeal carcinomatosis. Contribution of cytology (author's transl)].

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Adenocarcinoma↗

PubMed1979

Simultaneous microscopic and biochemical findings in breast carcinoma. Preliminary results.

Intratumoral protein and glucose phosphate isomerase (GPI) content as well as median nuclear DNA amount were determined in breast carcinoma that could be classified by Bloom's grading. These data were analyzed in comparison with TNM classification. Higher protein contents have been displayed in T2 or N+ breast cancers than in T1 or N- tumors. Bloom's grading is strongly correlated to median nuclear DNA content and to some extent with protein and GPI amount. With these results, we have to think about the value of prognostic cytologic criteria. The relationship between intratumoral protein content and prognostic clinical or histological data requires our attention. This would seem to dictate a need for caution in expressing the results of some variables in function of protein content.

Adult↗

PubMed1978