Search

The combination of high-dose folinic acid with 5-fluorouracil has shown improved response rates in several trials in advanced colorectal carcinoma. This however is at the expense of increased toxicity: regimens using weekly bolus injections produce diarrhoea in most patients and occasional toxic deaths from this, whilst those using daily injections for one week in four report both diarrhoea and severe oral mucositis. Both types of regimen have significant rates of myelosuppression. A recent report described a different schedule of 5-fluorouracil and folinic acid, which appeared better tolerated but equally active (De Gramont et al., 1988). Here we report results using the same programme, in 64 patients with advanced adenocarcinomas. (Forty three colorectal, ten gastric, six pancreatic and five of unknown primary.) Patients received 200 mg m-2 folinic acid by infusion over 2 h followed by an IV bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 400 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for a total of six to 12 courses depending upon the response. The overall response rate was 26% in 62 evaluable patients. No toxicity greater than WHO Grade II occurred. Diarrhoea and mucositis did occur in around 10% of treatments but were not troublesome. No febrile neutropenic episodes were seen. Despite previous reports which described only modest activity for this combination against stomach cancers, this regimen demonstrates low toxicity but retains good activity in the palliative treatment of both gastric and colonic adenocarcinomas.

Summary Two patients with Hodgkin's disease and cryptococcal meningitis are described. Both patients were treated with a combination of the two antifungal agents, amphotericin B and flucytosine. Nephrotoxicity was easily reversible in both patients and clinical improvement was seen with this combination therapy. Intrathecal therapy with amphotericin B was used in both patients. The optimal treatment of this disease may prove to be a combination of oral flucytosine, with amphotericin B given by intrathecal injection as well as rapid low dose intravenous injection.

In a multicentre study, 824 patients with operable rectal cancer were randomized to receive surgery alone, surgery plus a single fraction of 500 rad (5 Gy) and surgery plus 2000 rad (20 Gy) in 10 equal daily, i.e. multiple, fractions. The ratio of abdominoperineal excision to anterior restorative operations was 3:1. There was no evidence of an increased morbidity or mortality following irradiation. The multiple fraction 2000 rad group had tumours which were significantly smaller than those of the other groups. There was also a reduction in the Dukes' C cases in the multiple fraction group. Neither the tumour size nor the lymph node status was altered in the single fraction group.

Summary. In answer to the need for a less time-consuming assay of erythropoietin, the establishment of an in-vitro method using foetal mouse liver cells is described. This could be completed in 26 hr and was capable of detecting erythropoietin in concentrations as low as 0.005 or less International Units/ml. It was found to be useful both for clinical measurements and as a system for the study of erythropoietin production.

Cardiopulmonary studies were performed in 12 patients with longstanding polycythaemia rubra vera. Lung function tests indicated an increase in physiological deadspace and evidence of mismatched ventilation/perfusion relationships. Pulmonary capillary blood flow was measured by the nitrous oxide-body plethysmograph technique and a high frequency phonocardiogram was recorded from the pulmonary area to indicate pulmonary valve opening. In 10 patients the lung blood flow studies were repeated 24 hr after a 11. venesection. In the pre-venesection studies the pulsatility index of capillary flow, expressed as the ratio of peak to mean flow rates, averaged 1·6:1. The pulmonary artery to capillary flow conduction time, measured from the time of pulmonary valve opening to the foot of the capillary flow pulse, averaged 94 msec. These values were markedly reduced from normal (2·0:1 and 160 msec respectively) and indicated elevated pulmonary vascular resistance and pulmonary artery pressure. Venesection produced no significant change in the flow conduction time (mean 107 msec; P>0·10) suggesting the presence of irreversibly stiffened pulmonary arterial walls. Venesection did, however, restore the pulsatility of the capillary flow pulse to a normal level (mean 2·0:1), suggesting that there is an additional reversible component to the elevated pulmonary vascular resistance.

A prospective, randomized, controlled study of adjuvant chemotherapy in operable gastric cancer was commenced in 1976. Four hundred and eleven patients have been randomized into 1 of 3 treatment groups. Group A received a placebo injection of intravenous normal saline (10 ml) at 3-week intervals. Group B received a 5-day induction course of 5-fluorouracil (5-FU), vincristine, cyclophosphamide, and methotrexate followed by 3-week intravenous injections of 5-FU and mitomycin C (MMC). Group C received 3-week intravenous injections of 5-FU and MMC. The treatment was to be given for 2 years. Patients were stratified for age, sex, preoperative duration of symptoms, and clinicopathological stage prior to randomization. At this interim analysis, preoperative duration of symptoms and clinicopathological stage were statistically significant prognostic factors (p=

Sixty-five patients with advanced colorectal cancer were randomised to one of two schedules of recombinant alpha-2 interferon (IFN). In the first study, 36 patients received single-agent IFN, either 50 X 10(6) U/m2 intravenously on 5 consecutive days every 4 weeks, or 20 X 10(6) U/m2 subcutaneously three times per week. No tumour responses were seen and toxicity was unacceptable. In the second study, 29 patients received IFN in two similar schedules, but the dose of IFN was reduced to 20 X 10(6) U/m2 per day in the intravenous arm and to 5 X 10(6) U/m2 per day in the subcutaneous arm. In addition these patients were administered intravenous 5-Fluorouracil (5-FU), 250-500 mg/m2 per day on the first 5 days of each 4-weekly cycle. Although the toxicity of this second study was tolerable, only one short-lived partial remission was observed. Alpha-2 interferon, alone or in combination with 5-FU, is ineffective in advanced colorectal cancer.

824 patients with operable rectal carcinoma were randomly allocated to be treated by surgery alone, 2000 rad in 10 daily fractions and 500 rad as a single fraction. No difference has been demonstrated in the actuarial survival rates to 5 years. The local recurrence-free and metastasis-free rates are similar in all groups. There is also no evidence that the pre-operative radiotherapy benefited patients in subgroups by Dukes' stage. The complication rates were also similar in the three treatment groups.

Summary. A case is described of a woman with polycythaemia secondary to a uterine fibromyoma. The polycythaemia disappeared after the removal of the tumour. The tumour tissue and also fluid from cysts within the tumour showed erythropoietic activity when estimated by the polycythaemic mouse assay employing two dose levels and a standard related to the WHO erythropoietin standard. It is suggested that polycythaemia in this case was caused by the production of erythropoietin and not by an indirect pressure effect from the tumour.

The presentation and management of a case of acute Listeria monocytogenes osteomyelitis in a lady with acute lymphoblastic leukaemia are described. The literature on Listeria infection is briefly reviewed, and the importance of scrutinizing diphtheroid-like isolates in the laboratory is stressed.