Combined-modality treatment of small-cell lung cancer: Randomized comparison of three induction chemotherapies followed by maintenance chemotherapy with or without radiotherapy to the chest

BACKGROUND: From 1980 to 1983 the Swiss Group for Clinical Cancer Research(SAKK) performed a randomised phase HI trial in patients withsmall-cell lung cancer with the objective of improving the resultsof induction chemotherapy and defining the role of consolidatingchest irradiation. PATIENTS AND METHODS: Patients were initially randomised to induction arms AVP (adriamycin,etoposide and cisplatin given every four weeks for four cycles),EVA (cyclophospha-mide, etoposide and adriamycin given everyfour weeks for four cycles) or MOC/AVP (methotrexate, vincristine,cyclo-phosphamide alternating with adriamycin, etoposide andcisplatin given for two cycles). All patients received prophylacticcranial irradiation with 30 Gy, and after four months of inductionchemotherapy were randomized to maintenance chemotherapy withor without consolidating chest irradiation. The patients inthe combined-modality maintenance arm first received radiationtherapy to the chest (45 Gy) followed by MOC/EVA chemotherapy. RESULTS: 266 patients were eligible and evaluable. An overall responserate of 70% with 21% of complete remissions, a median survivalof 9.3 months and survival of 8% of the patients at two yearswere observed. The highest objective response rate was achievedwith the AVP-induction chemotherapy with an 80% response rateand 32% complete remissions. Similar results were achieved withthe alternating regimen of MOC/AVP. In contrast, patients treatedwith the EVA induction regimen had significantly lower overallremission (56%) and complete remission rates (7%). The roleof consolidating chest irradiation could not be clarified inlimited-disease patients due to the small number of them whowere randomised to the maintenance part of the study. However,in patients with extensive disease in partial remission afterinduction treatment, combined maintenance therapy had a moresignificant adverse effect on survival than maintenance chemotherapyalone (median survival in the maintenance phase of 148 daysversus 239 days, p = 0.011). CONCLUSION: We conclude that the combination of adriamycin, etoposide andcisplatin is an active induction treatment. Consolidating chestirradiation is contraindicated in patients with extensive diseasein partial remission after induction when given in a sequentialmanner, as in our trial. small-cell lung cancer, chemotherapy, alternating chemotherapy, combined-modality treatment, radiotherapy     

Development of a special balloon occlusion device to prevent adverse events in high-risk patients during open aortic surgery

OBJECTIVE: To prevent clamp injury that may occur during aortic surgery, we aimed to develop a special balloon occlusion (BO) device to lower the thromboembolic risk in patients with severe atherosclerosis during aortic aneurysm repair. METHODS: The study comprised two test phases: a laboratory-testing series focussing on flexible artificial aortas, and an experimental series conducted on 10 pigs. RESULTS: The device proved to be effective during the laboratory tests and the experiments on pigs. No complications such as intraoperative balloon rupture, dislocation, or occlusion leaks occurred. No damage to the aortic vessels was observed in further histological examinations. CONCLUSIONS: This BO device has the potential to become an alternative to cross-clamping for vascular surgeons in patients with severely atherosclerotic vessels.     

Implantation of the permanent Jarvik-2000 left-ventricular-assist-device: surgical technique.

The Jarvik-2000 is an axial-flow left-ventricular-assist-device (LVAD) designed for permanent use. The power supply is provided by a cable plugged into a skull-pedestal mounted in the retro-auricular area. We describe the surgical technique and discuss potential and encountered problems.     

Combination chemotherapy with mitomycin, vindesine, and cisplatin for non-small cell lung cancer. Association of antitumor activity with initial tumor burden and treatment center

From 1984 through 1986, 205 patients with non-small cell lung cancer were entered into a group-wide trial of the Swiss Group for Clinical Cancer Research (SAKK). This trial evaluated the combination of mitomycin (8 mg/m2 intravenously [IV] on day 1), vindesine (3 mg/m2 IV on days 1 and 8), and cisplatin (60 mg/m2 IV on day 1) with forced diuresis, repeated every 4 weeks (MiViP regimen). One hundred eighty-three patients were evaluable. Six complete and 69 partial responses were documented for an overall response rate of 41% (95% confidence interval, 34% to 50%). In the multivariate analysis the strongest predictors for response were the participating institution and the number of initially involved organ sites. The estimated median time to progression for patients with a complete response, partial response, or stable disease was 155 days (estimated inter-quartile range, 99 to 258 days). In the multivariate analysis the time to progression was significantly associated with the number of involved organ sites (P = 0.041). The estimated median survival time for the 183 evaluable patients was 239 days (estimated inter-quartile range, 137 to 436 days). In univariate and multivariate analyses performance status, number of involved organ sites, pretreatment status with radiation therapy, and participating institution were all significantly associated with survival. The principal toxicities were myelosuppression and nausea and vomiting with 16% of the patients refusing further treatment after a median of four cycles of chemotherapy. In conclusion, the MiViP regimen was an active combination chemotherapy in patients with non-small cell lung cancer in a large trial performed by the SAKK. The prognostic value of the participating institution and the number of organ sites involved by metastatic deposits in non-small cell lung cancer needs further investigation.     

Phase II study of 5′-deoxy-5-fluorouridine (doxifluridine) in advanced malignant melanoma

Summary Forty-two patients with malignant melanoma were treated with doxifluridine, 4000 mg/m² daily ×5, repeated every 3 weeks. The daily dose was reduced to 3000 mg/m² in patients who had experienced severe myelosuppression with prior chemotherapy. A total of 35 patients were evaluable for response, and 25 of these received two or more courses. Two responses were observed. Toxicity mainly took the form of nausea, vomiting, stomatitis, dizziness, ataxia, and fatigue. Mild leukopenia was frequent (43%). Nadir counts <1.5×10⁹/l leukocytes or 50×10⁹/l platelets were seen in 7% and 2% of the courses respectively. Doxifluridine has no useful activity against malignant melanoma.     

Blood cardioplegia filtration

The introduction of blood cardioplegia has been proven to limit ischaemia and reperfusion injury in cardiac surgery. But the presence of activated neutrophils in the capillary bed may cause further damage. Leukocyte filters have been shown to be very effective in reducing the leukocytes in blood cardioplegia to less than 10%. Leukocyte depletion of blood cardioplegia provides an excellent approach to minimizing myocardial injury, predominantly in high-risk cardiac surgery.     

Human Pharmacology of Cefotaxime (HR 756), a New Cephalosporin

Cefotaxime (HR 756) is a new semisynthetic parenteral cephalosporin with exceptional activity against gram-negative organisms and considerable stability against their beta-lactamases. To study its pharmacokinetic properties, 0.5-, 1-, and 2-g doses were administered to each of six volunteers intravenously over 15 min, followed by a sustaining infusions of 0.5, 1, and 2 g/h, respectively, for 3 consecutive hours. The loading doses produced mean peak levels of 41, 93, and 160 mug/ml, and mean steady-state serum concentrations were 27, 64, and 138 mug/ml, respectively. The mean terminal half-life was 75 +/- 7 min. The total volume of distribution averaged 0.22 +/- 0.03 liters/kg of body weight. Total body and renal clearances were 232 +/- 30 and 145 +/- 24 ml/min per 1.73 m(2), respectively; 63 +/- 9% of the administered dose was excreted through the kidneys in 24 h. To determine the effect of cefotaxime on the renal tubules, urinary alanine aminopeptidase excretion was measured before, during, and after the infusions. It remained within the normal range in all instances; however, 48 +/- 14% of the total daily alanine aminopeptidase output was recovered during the infusion period. Side effects were dose related and included fatigue, loose stools, and night sweats. No significant changes in hematology, serum chemistry, or urinalysis were recorded.