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Summary The monoclonal antibody A33 recognises a tumour-associated antigen on human colorectal carcinoma, and has undergone preliminary evaluation in the clinic where selective localisation to

The predictive value of serum alkaline phosphatase (SAP) and of prostatic acid phosphatase (PAP) for response to treatment (NPCP criteria) was retrospectively assessed in patients with bone metastases from prostate cancer. Fifty-one patients had SAP measured at the start of treatment and at 1 and 2 months. In 31 of these, corresponding PAP levels were also available at each time point. SAP/PAP profiles at 2 months were classified as "increased" (increment 15% or greater), "decreased" (reduction greater than 15%) or "stable", compared with baseline levels. An additional category, SAP "flare", was also identified (SAP increment greater than 15% at 1 month, with subsequent fall at 2 months). There was a strong association between the SAP profile at 2 months and the response category, whereas the PAP profile at 2 months was more weakly associated. Using results from the 31 patients with both SAP and PAP profiles, the level of SAP was significantly better in predicting the category of response (SAP: sensitivity 94%, specificity 79%; PAP: sensitivity 53%, specificity 57%). An SAP "flare" was associated with response in 8 of 12 patients. An increase in SAP at 1 month is therefore a poor guide to progressive disease and should not be used in isolation to discontinue treatment early. The SAP profile is of value as an earlier predictor of response than X-rays or bone scans and is more reliable than the PAP profile in monitoring patients with prostate cancer and bone metastases.

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Long-term disease-free survival (78 + and 31 + months) has been achieved in two of four patients treated for brain metastases from non-seminomatous germ cell tumours between 1980 and 1984. The incidence of cerebral metastases among 101 patients seen over the 5-year period was 4%. The encouraging results from the use of combined modality treatment, incorporating cisplatin-based chemotherapy, whole brain irradiation and surgery, are reviewed.

Summary Amphethinile is a new spindle poison with a novel structure that has shown activity in the L1210, ADJ/PC6 and Walker carcinoma rodent tumours. In addition the agent appeared to have an improved therapeutic ratio compared to existing spindle poisons and is well absorbed when administered orally. The starting dose for the phase I study was 40mgm 2 (1/10th mouse LD10) and further patients were studied at 200, 400, 800 and 1200 mgm2, dose escalation being based on pharmacological monitoring. Significant toxic effects were seen only at 800 and 1200mgm-2. At these doses patients experienced nausea and vomiting, light headedness during the infusion and varying degrees of lethargy following therapy. Two of six patients at 800 mgm 2 developed severe pain in the tumour bearing area 1-2 h after treatment and one experienced colicky abdominal pain. At 1200 mgm-2 two patients died within 48 h of treatment from what appeared to be vascular causes. Following these episodes the trial was discontinued. Neutropenia and alopecia occurred in two patients, one at 800 and one at 1200 mgm 2. These patients achieved the highest drug exposure in terms of area under the concentration x time curve.It was not possible to achieve an AUC consistently high enough to produce cytotoxic effects due to the occurrence of dose limiting toxicities thus amphethinile cannot at present be recommended for phase II testing by the i.v. route.The dose escalation scheme based on pharmacological monitoring resulted in a considerable saving in the duration of the trial. Further evaluation of this methodology is recommended.Amphethinile (ICI 134154, CRC 82/07) is a novel compound (Figure 1) which was first synthesised by ICI plc (Alderley Park, Cheshire) and aroused interest when it was shown to terminate pregnancy in rats. This effect occurred following two injections on day 9 of gestation or one on day 10 and the qualitative appearance of the degenerating implants suggested that it might be due to cytotoxic damage. The drug was fully effective both orally and subcutaneously at a dose of 5 mgkg-1 and produced other toxic effects at a dose of 25mg kg-1, suggesting a therapeutic ratio of -5:1. Experiments with HeLa cells indicated that amphethinile was acting as a spindle poison and in similar experiments on pregnant rats vincristine was shown to have a therapeutic ratio of 2-3:1. These results suggest that amphethinile may have an improved therapeutic ratio compared to vincristine.The compound was submitted to the NCI pre-clinical screen and was shown to be active in L1210, ADJ/PC6 and the Walker carcinoma but inactive in the TLX/5 and GHSPit tumours.In view of this pre-clinical activity, the possible improvement in therapeutic ratio compared with existing spindle poisons and the good oral absorption, the drug was taken up by the CRC Phase I/II committee for formulation and pre-clinical toxicology.Amphethinile was found to be extremely insoluble in aqueous solution (2.5 ppm at 20°C and 6 ppm at 37°C). Moreover the use of polar solvents carries a risk o...