Diana Brinkley

Quadruple chemotherapy versus radiotherapy in treatment of primary hepatocellular carcinoma.

Although there have been many therapeutic trials of chemotherapy for primary hepatoma, few have been controlled and the results of treatment have been disappointing. The present report is concerned with a controlled trial of chemotherapy alone versus radiotherapy followed by chemotherapy in 18 patients with primary hepatoma. Ten patients received quadruple chemotherapy (5‐flurouracil, cyclophosphamide, methotrexate, and vincristine). These patients survived considerably longer (21 weeks) than eight patients who received radiotherapy followed by the same chemotherapy regime (12 weeks). Further analysis of these results suggested that length of survival in both treatment groups was related to age, length of history, levels of serum bilirubin and aspartate transaminase, and to the presence of cirrhosis or ascites. According to these criteria, patients were subdivided into two grades of disease. For patients with less severe disease (grade A), median survival after chemotherapy alone (54 weeks) was longer than after radiotherapy followed by chemotherapy (24 weeks). Survival of patients with severe disease (grade B) was equally poor in both treatment groups (5 weeks, chemotherapy; 7.5 weeks radiotherapy followed by chemotherapy). In conclusion, these results show that quadruple chemotherapy alone is a valuable form of therapy for grade A patients. Neither form of therapy, however, was of any benefit for grade B patients. Cancer 40:609–614, 1977.

TREATMENT OF HIGH BILEDUCT CARCINOMA BY INTERNAL RADIOTHERAPY WITH IRIDIUM-192 WIRE

Abstract Eight patients with high bileduct carcinoma were treated by a new technique of internal radiotherapy with iridium-192 wire after biliary drainage had been established. Seven patients had satisfactory initial biliary drainage, and six patients are still alive 11 months (median time) after treatment. The procedure produced no systemic side-effects and it prolonged survival in patients in whom restoration of bile drainage had been satisfactory.

Internal biliary drainage and local radiotherapy with iridium-192 wire in treatment of hilar cholangiocarcinoma

Curative surgery is not possible in the vast majority of patients who present with hilar cholangiocarcinoma. Palliative therapy to relieve jaundice, either at laparotomy or percutaneously, is therefore necessary. The mean survival of these patients is of the order of 8.5 months (Wheeler et al., 1981). We report a significant increase in mean survival to 16.8 months in patients treated with internal biliary drainage when combined with local irradiation to the tumour with iridium-192.

Combined treatment of soft tissue and osteosarcomas by radiation and ICRF 159

In a pilot clinical assessment of combined radiotherapy with the antimitotic agent ICRF 159, a good response was obtained in 18 of 22 patients (82%) with soft tissue and bone sarcomas. Six patients had complete regressions and 12 had regressions of 50% or more. Two had regressions of less than 50% and only 2 showed no response. Severe toxicity requiring interruption of treatment was not observed, but skin reactions were greater than expected. No lung reactions were seen. The combination appears to be synergistic.

A toxicity study of recombinant interferon-gamma given by intravenous infusion to patients with advanced cancer.

SummaryEighteen patients with solid tumours were treated with human recombinant interferon-gamma at escalating dose levels starting at 1×106 units/m2 per infusion and rising through 3×106, 6×106, 9×106 and 22×106 to a maximum of 110×106 units/m2 per infusion. The IV infusions were given three times a week over a 4-week period.Side effects were seen in all patients, but were mild except at the highest dose. Acute dose-related effects included pyrexia, tiredness, thirst, chills and rigors. Chronic dose-related effects included anorexia, lethargy, weakness, disorientation, a trace of proteinuria and minimal rises in liver enzymes. In addition, effects were observed which were not related to dose. These included headache, nausea and vomiting, backache, myalgia, flatulence and a mild, transient reduction in neutrophils and erythrocytes.At the highest dose level dose-limiting toxicity was observed, consisting in severe tiredness and anorexia, hypotension, disorientation and changes on the electrocardiograph.Overall, toxicity was similar to that seen with preparations of interferon-alpha, except that no tolerance to the effects of interferon-gamma was noted. We observed less hepatic and haematological toxicity, but also recorded flatulence, handcramps and electrocardiograph changes, which have not been reported with interferon-alpha.When given according to this regimen, doses of 22×106 units/m2 per infusion of recombinant interferon-gamma were generally well tolerated by the patients.

COMPARISON OF 5-DAY, 1-DAY, AND 2-DAY CYCLICAL COMBINATION CHEMOTHERAPY IN ADVANCED BREAST CANCER

The results of 5-day cyclical combined chemotherapy for advanced breast cancer were compared in two trials with the less demanding 1-day and 2-day regimens. At all stages, except at 3 months, 5-day treatment was significantly more successful in providing regression and remission of tumours than the 1-day regimen. However, although the differences are not statistically significant, data from the second trial indicated that the 2-day regimen tended to be more effective than the 5-day regimen. The lower 95% confidence limit for the success of the 2-day treatment was 56.2% at 3 months.

Local Radiotherapy of Biliary Malignancies

Patients presenting with obstructive jaundice due to a cholangiocarcinoma involving the hilum of the liver pose a major problem in management. Despite recent advances in preoperative assessment of resectability and in operative techniques (Blumgart 1978; Williamson et al. 1980), in most reports the rate of attempted radical curative resection has remained very low (Inouye and Whelan 1978; Akwari and Kelly 1979; Evander et al. 1980; Blumgart 1982) and the operative mortality is still 10%–20% (Lannois et al. 1979; Evander et al. 1980). In contrast, effective palliation can often be achieved with low operative mortality if the obstruction is relieved by a cholangioenteric anastamosis (Cahow 1979) or by operative insertion of a transhepatic U tube (Terblanche et al. 1972).