ABSTRACT
Despite chemotherapy, median survival of patients with advanced pancreatic cancer (APC) remains poor. Gemcitabine (GEM) remains standard treatment. Numerous phase II studies have suggested that combination therapies may improve response rates. Mitomycin C (MMC) when used as a single agent may have response rates comparable to other cytotoxic drugs. Therefore, MMC could be an interesting drug to be combined with GEM. This study aimed to assess the feasibility, toxicity and efficacy of GEM combined with MMC in patients with APC. Between April 1997 and January 2002, 55 consecutive patients were treated with GEM 800 mg/m2 i.v., days 1, 8 and 15, and MMC 8 mg/m2 i.v., day 1, every 4 weeks in an outpatient setting. Patient characteristics included: M/F 34/21, median age of 58 years, ECOG PS 0-2. A median of 3 cycles was administered. The most frequent toxicity was thrombocytopenia grade III/IV in 54% of patients. Ten patients experienced dyspnea+/-X-ray-proven pneumonitis (n=2). One of these patients developed a hemolytic uremic syndrome after the sixth application of MMC. There was one early death as a consequence of a stroke. The objective response rate was 29% (95% confidence interval: 17-43). Eighteen patients had stable disease resulting in an overall tumor growth control of 62%. Time to progression was 4.7 months and median overall survival was 7.25 months. We conclude that, except for thrombocytopenia, the combination of GEM and MMC is well tolerated. These results compare favorably to single-agent chemotherapy with GEM or the combination of 5-fluorouracil plus MMC. Furthermore, this regimen is cost-effective and, since it can be given on an outpatient basis, contributes to the quality of life.
Subject(s)
Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Mitomycin/therapeutic use , Pancreatic Neoplasms/drug therapy , Severity of Illness Index , Aged , Antineoplastic Combined Chemotherapy Protocols , Clinical Trials, Phase III as Topic , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Disease Progression , Drug Administration Schedule , Dyspnea/chemically induced , Dyspnea/complications , Female , Follow-Up Studies , Hematologic Diseases/chemically induced , Hematologic Diseases/complications , Hematologic Diseases/mortality , Hospitals, University , Humans , Injections, Intravenous , Male , Middle Aged , Mitomycin/administration & dosage , Mitomycin/adverse effects , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Pneumonia/chemically induced , Pneumonia/complications , Randomized Controlled Trials as Topic , Treatment Outcome , GemcitabineABSTRACT
BACKGROUND: High-dose chemotherapy followed by transplantation of autologous haemopoietic stem cells (BEAM-HSCT) is frequently used to treat patients with relapsed Hodgkin's disease. We aimed to compare this treatment with conventional aggressive chemotherapy without stem-cell transplantation (Dexa-BEAM). METHODS: 161 patients between 16 and 60 years of age with relapsed Hodgkin's disease were randomly assigned two cycles of Dexa-BEAM (dexamethasone and carmustine, etoposide, cytarabine, and melphalan) and either two further courses of Dexa-BEAM or high-dose BEAM and transplantation of haemopoietic stem cells. Only patients with chemosensitive disease (complete or partial remission after two courses of Dexa-BEAM) proceeded to further treatment. The primary endpoint was freedom from treatment failure for patients with chemosensitive disease. Analysis was per protocol. FINDINGS: 17 patients were excluded from the study after randomisation (ten given Dexa-BEAM and seven given BEAM-HSCT). Median follow-up was 39 months (IQR 3-78). Freedom from treatment failure at 3 years was significantly better for patients given BEAM-HSCT (55%) than for those on Dexa-BEAM (34%; difference -21%, 95% CI -39.87 to -2.13; p=0.019). Overall survival of patients given either treatment did not differ significantly. INTERPRETATION: High-dose BEAM and transplantation of haemopoietic stem cells improves freedom from treatment failure in patients with chemosensitive first relapse of Hodgkin's disease irrespective of length of initial remission.
