Combination Maintenance Therapy Research Articles

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

From 1980 to 1983 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with small-cell lung cancer with the objective of improving the results of induction chemotherapy and defining the role of consolidating chest irradiation. Patients were initially randomised to induction arms AVP (adriamycin, etoposide and cisplatin given every four weeks for four cycles), EVA (cyclophosphamide, etoposide and adriamycin given every four weeks for four cycles) or MOC/AVP (methotrexate, vincristine, cyclophosphamide alternating with adriamycin, etoposide and cisplatin given for two cycles). All patients received prophylactic cranial irradiation with 30 Gy, and after four months of induction chemotherapy were randomized to maintenance chemotherapy with or without consolidating chest irradiation. The patients in the combined-modality maintenance arm first received radiation therapy to the chest (45 Gy) followed by MOC/EVA chemotherapy. 266 patients were eligible and evaluable. An overall response rate of 70% with 21% of complete remissions, a median survival of 9.3 months and survival of 8% of the patients at two years were observed. The highest objective response rate was achieved with the AVP-induction chemotherapy with an 80% response rate and 32% complete remissions. Similar results were achieved with the alternating regimen of MOC/AVP. In contrast, patients treated with the EVA induction regimen had significantly lower overall remission (56%) and complete remission rates (7%). The role of consolidating chest irradiation could not be clarified in limited-disease patients due to the small number of them who were randomised to the maintenance part of the study. However, in patients with extensive disease in partial remission after induction treatment, combined maintenance therapy had a more significant adverse effect on survival than maintenance chemotherapy alone (median survival in the maintenance phase of 148 days versus 239 days, p = 0.011). We conclude that the combination of adriamycin, etoposide and cisplatin is an active induction treatment. Consolidating chest irradiation is contraindicated in patients with extensive disease in partial remission after induction when given in a sequential manner, as in our trial.

Valproic acid disposition in epileptic patients during combined antiepileptic maintenance therapy.

A previously developed mass spectrometric method was used to measure, in the presence of the unlabeled drug, the fate of pulse dose of tetradeuterated valproic acid given to epileptic patients. By this means the disposition of valproic acid (VPA) was studied in several epileptic patients on maintenance therapy with VPA and at least one other anti-epileptic drug. For 6 patients with 6 different anti-epileptic drug combinations, the mean VPA half-life was only 6.2 h, as compared to about 15 h after a single dose. The mean plasma clearance in those patients was 16.4 ml/min. The volume of distribution was 0.14 l/kg, which did not differ from values found in single dose studies. The clinical relevance of these findings is pointed out.