ABSTRACT
BACKGROUND: Bendamustine is a drug with a favorable side effect spectrum and it offers a chance to overcome tumor resistance in pretreated patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Bendamustine was given as flat dose with 200 mg at days 1 + 2 in MBC patients pretreated with 2-3 different chemotherapies. Therapy was repeated at day 28 or fully recovered neutrophils. After 2 treatment cycles, a tumor response evaluation was performed. Toxicity was graded according to the National Cancer Institute common toxicity criteria (NCI-CTC) catalogue. RESULTS: 22 patients were evaluated for toxicity. 4 patients dropped out before the first tumor response evaluation; thus, 18 patients were evaluable for anticancer efficacy evaluation. 3/18 patients reached a partial remission (PR), 4 stable disease and 11 showed progression after 2 treatment cycles. The time to progression (TTP) was 5 months in patients with PR and 4 months in patients with no change (NC). In patients with progressive disease (PD), TTP was < 2 months. The main toxicities were nausea, weight loss and fatigue. CONCLUSIONS: Bendamustine can be given with a fixed flat dose, which simplifies the drug preparation. 2/5th of all treated patients responded to this therapy whereas bendamustine showed no anticancer effect in 3/5th of all patients. Bendamustine is definitely a drug with anticancer potential.
Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/secondary , Nitrogen Mustard Compounds/administration & dosage , Adult , Aged , Antineoplastic Agents/administration & dosage , Bendamustine Hydrochloride , Dose-Response Relationship, Drug , Female , Germany , Humans , Middle Aged , Nitrogen Mustard Compounds/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: Combined therapy of continuous low dose capecitabine and high dose celecoxib targeting angiogenesis was used in a phase II trial to treat advanced cancer patients. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to monitor antiangiogenic effects. MATERIAL AND METHODS: 37 Patients (21 men, 16 women), mean age 60 years, with advanced and progressive cancer of various tumor types were included. Therapy consisted of 2 x 500 mg oral capecitabine/ day and 2 x 400 mg oral celecoxib/day continuously until progression of disease. To monitor antiangiogenic effects, DCE-MRI measurements were performed at baseline, after 1 month, and after 3 months of therapy. Tumor assessment was performed according to RECIST criteria, toxicity was evaluated according to the CTC version 2.0 catalogue. RESULTS: Therapy was well tolerated without grade 3 and 4 toxicities. The mean number of treatment cycles was 4 (range: 1-15+). Disease stabilization after 3 cycles was seen in 11 patients. 6 patients were stable over long periods. The mean number of treatment cycles in this group was 10 (range: 7-15+). DCE-MRI demonstrated a reduction of tumor vessel permeability and blood flow in patients who reached stable disease or some minor regression. CONCLUSION: Continuous dosing of the combination of capecitabine and celecoxib was well tolerated, produced antiangiogenic effects, and has antitumor activity. Patients with rapid progression did not benefit.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Neoplasms/drug therapy , Neovascularization, Pathologic/drug therapy , Pyrazoles/administration & dosage , Sulfonamides/administration & dosage , Administration, Oral , Angiogenesis Inhibitors/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine , Celecoxib , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Neoplasms/blood supply , Pyrazoles/adverse effects , Sulfonamides/adverse effects , Treatment OutcomeABSTRACT
PURPOSE: The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH) is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that shows superior antitumor efficacy in murine tumor models and a favorable toxicity profile in mice, rats, and dogs compared with doxorubicin. The purpose of the phase I study was to characterize the toxicity profile of DOXO-EMCH, establish a recommended dose for phase II studies, and assess potential anticancer activity. EXPERIMENTAL DESIGN: A starting dose of 20 mg/m2 doxorubicin equivalents was chosen. Forty-one patients with advanced cancer disease were treated with an i.v. infusion of DOXO-EMCH once every 3 weeks at a dose level of 20 to 340 mg/m2 doxorubicin equivalents. RESULTS: Treatment with DOXO-EMCH was well tolerated up to 200 mg/m2 without manifestation of drug-related side effects. Myelosuppression (grade 1-2) and mucositis (grade 1-2) were the predominant adverse effects at dose levels of 260 mg/m2 and myelosuppression (grade 1-3) as well as mucositis (grade 1-3) were dose limiting at 340 mg/m2. No cardiac toxicity was observed. Of 30 of 41 evaluable patients, 12 patients (40%) had progressive disease, 15 patients (57%) had stable disease, and 3 patients (10%) had a partial remission. CONCLUSIONS: DOXO-EMCH showed a good safety profile and was able to induce tumor regressions in tumor types known to be anthracycline-sensitive tumors, such as breast cancer, small cell lung cancer, and sarcoma. The recommended doxorubicin equivalent dose for phase II studies is 260 mg/m2.
