Cyclosporin plus doxorubicin, vincristine and etoposide in the treatment of refractory non-Hodgkin's lymphoma: A phase II study

In an attempt to circumvent clinical multidrug resistance, we conducted a Phase II trial of cyclosporin plus combination chemotherapy in patients with relapsed or refractory non-Hodgkin's lymphoma. Thirteen patients, all of whom had been previously treated with a doxorubicin-containing regimen, received doxorubicin 50 mg/m² intravenous continuous infusion (IVCI) over 96 h (days 1-4), vincristine 2 mg i.v. (day 1), and etoposide 75 mg/m² i.v. daily for 4 days (days 1-4). Four days prior to chemotherapy, patients received a loading dose of cyclosporin (0.88 mg/kg i.v. over 2 h), followed by a maintenance dose (1.8 mg/kg per day IVCI for 9 days). Cyclosporin dose escalation was permitted, conventionally defined therapeutic levels of cyclosporin were achieved; this drug was well tolerated at these doses. The study was closed due to a poor response rate; only one patient achieved a complete remission of 33 weeks' duration. Grade 3 and 4 toxicities included gastrointestinal haemorrhage (one patient), sensory neuropathy (two patients), stomatitis (two patients), and transaminase elevation (one patient). Asymptomatic grade 1-2 toxicities (elevated creatinine and transaminase levels) occurred in 33% of patients. There were no treatment associated deaths. Prolonged neutropenia and thrombocytopenia were the primary haematological toxicities. Although the addition of cyclosporin at this dose and schedule did not improve response rates in this patient group, future trials using higher doses of cyclosporin with combination chemotherapy may warrant further investigation.