amrubicin and Alopecia

The purpose of this investigator-initiated multicenter phase II study was to determine the activity of the third-generation synthetic anthracycline, amrubicin, administered as second-line therapy in patients with advanced urothelial carcinoma.. Patients with progressive metastatic urothelial cancer despite first-line chemotherapy were eligible for enrollment. Amrubicin was initially administered at a dose of 40 mg/m(2)/day daily × 3 every 21 days, and the dose was subsequently reduced to 35 mg/m(2)/day daily × 3 every 21 days. Prophylactic granulocyte colony-stimulating factor was administered to all patients, and prophylactic antibiotics were administered to patients at high risk of febrile neutropenia. Treatment was administered for up to six cycles in the absence of intolerable toxicity or disease progression. The primary endpoint was the objective response rate.. A total of 22 patients were enrolled. Among the first three patients enrolled, all developed grade 4 neutropenia and one patient died of neutropenic sepsis. The starting dose of amrubicin was subsequently reduced, there were no further episodes of febrile neutropenia, and only one patient required a subsequent dose reduction. The most common adverse events were hematologic; grade ≥3 neutropenia occurred in 27 %, and other grade ≥3 adverse events were uncommon. Partial responses were achieved in three patients [13.6, 95 % confidence interval (CI) 0-28 %), while stable disease was the best response in 12 patients (54.5, 95 % CI 33.7-75.3 %). The trial was closed prematurely due to a development decision by the funder.. Amrubicin as second-line therapy in advanced urothelial carcinoma is associated with modest single-agent activity. While there remains a role for the introduction of novel cytotoxic agents in the management of metastatic urothelial cancer, optimal development of such therapies will likely require patient selection biomarkers.

Topics: Aged; Alopecia; Anthracyclines; Antineoplastic Agents; Drug Administration Schedule; Fatigue; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Middle Aged; Nausea; Thrombocytopenia; Topoisomerase II Inhibitors; Treatment Outcome; Urologic Neoplasms

A late phase II clinical trial of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, was conducted at 14 institutions nationwide, in patients with non-Hodgkin's lymphoma. In this multi-center collaborative study, doxorubicin hydrochloride was replaced by amrubicin hydrochloride in CHOP therapy, a standard regimen for non-Hodgkin's lymphoma consisting of cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisolone. A total of 39 patients were enrolled in this study between January 1996 and March 1998. Among them, 37 patients were eligible for this study. The study drugs were administered to patients with non-Hodgkin's lymphoma according to the following schedule: amrubicin hydrochloride (100 mg/m2, body surface area), cyclophosphamide (750 mg/m2) and vincristine sulfate (1.4 mg/m2, a maximal dose of 2.0 mg/body) were administered intravenously on day one, while prednisolone (60 mg/m2/day) was administered orally on days 1 to 5. This cycle of treatment was repeated every three weeks in principle. The efficacy and safety were assessed for 37 eligible patients. The combined rate for CR + CRu was 70.3% (26/37) and the overall response rate (CR + CRu + PR) was 86.5% (32/37). demonstrating that amrubicin hydrochloride was very effective in the treatment of non-Hodgkin's lymphoma. The most frequent adverse reactions that occurred during the study were myelosuppressions: leukopenia and neutropenia, 100% (37/37); and decreases in hemoglobin levels, 81.1% (30/37). Thrombocytopenia, elevations of serum GOT and GPT levels, anorexia, nausea/vomitting, fever, stomatitis and alopecia were also observed. Although leukopenia and neutropenia of grade 3 or higher were noted in 89.2% (33/37) and 94.6% (35/37), respectively, they were controllable by administrations of G-CSF or solely by follow-up observations. One patient developed intestinal paralysis (grade 4) and another developed hematemesis. In conclusion, these results indicate that amrubicin hydrochloride is an effective agent as a component of combination chemotherapy for non-Hodgkin's lymphoma.

Topics: Aged; Alopecia; Anorexia; Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Drug Administration Schedule; Female; Humans; Leukopenia; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisolone; Survival Rate; Thrombocytopenia; Vincristine; Vomiting, Anticipatory