amrubicin and Nausea

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

Amrubicin is active in the treatment of extensive-disease small cell lung cancer (ED-SCLC), and carboplatin is an analogue of cisplatin with less non-hematological toxicity.. The purpose of this study was to determine the efficacy and toxicity of amrubicin and carboplatin combination chemotherapy for previously untreated patients with ED-SCLC.. Eligibility criteria were chemotherapy-naïve ED-SCLC patients, performance status 0-1, age ≤75, and adequate hematological, hepatic and renal function. Based on the phase I study, the patients received amrubicin 35 mg/m(2) i.v. infusion on days 1, 2, and 3, and carboplatin AUC 5 i.v. infusion on day 1. Four cycles of chemotherapy were repeated every 3 weeks.. Thirty-five patients were enrolled, and 34 patients were eligible and assessable for response, toxicity, and survival. Patients' characteristics were as follows: male/female = 26/8; performance status 0/1 = 4/30; median age (range) = 64 (41-75); stage IV = 34. Evaluation of responses was 6 complete response, 21 partial response, and 7 stable disease (response rate 79.4 %, 95 % CI 63.6-88.5 %). Grade 3 and 4 leukopenia, neutropenia, and thrombocytopenia occurred in 59, 82, and 26 %, respectively. There were no treatment-related deaths or pneumonitis. Three patients experienced hypotension as an amrubicin infusion reaction. The median progression-free survival time was 6.5 months. The median overall survival time and 1-, 2-, and 3-year survival rates were 15.6 months, and 63, 28, and 7 %, respectively.. Amrubicin and carboplatin were effective and tolerable as chemotherapy for previously untreated patients with ED-SCLC. Further investigation of amrubicin and carboplatin is warranted.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Neutropenia; Small Cell Lung Carcinoma; Treatment Outcome

A single-center phase I trial was designed to determine both the dose-limiting toxicities and the maximum tolerated dose (MTD) for amrubicin hydrochloride in combination therapy with cisplatin for advanced non-small cell lung cancer (NSCLC) patients with prior chemotherapy.. Eligible patients received amrubicin and cisplatin on days 1 through 3 every 3 or 4 weeks. Cisplatin was administered at a fixed dosage of 20 mg/m(2) while the administered dose of amrubicin was started at 20 mg/m(2). Each group comprised 3 or 6 patients. When dose limiting toxicities were noted in three or more of six patients at a particular level, that level was estimated to be the MTD.. Fifteen patients were enrolled in this study, including 5 males and 10 females, with a median age of 57. The dose limiting toxicities included grade 4 neutropenia which lasted 4 or more days and febrile neutropenia. The non-hematologic toxicities were well managed and rarely severe. The MTD of amrubicin in this combination regimen was estimated to be 30 mg/m(2).A partial response was observed in 4 of 15 patients (27%).. The recommended dose was thus determined to be 25 mg/m(2) amrubicin with 20 mg/m(2) cisplatin for 3 consecutive days. A phase II study is currently underway.

Topics: Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Female; Fever; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neutropenia; Vomiting, Anticipatory

Although amrubicin hydrochloride (AMR) has promising activity against pretreated lung cancer, there are few reports on the adverse events of this agent in a clinical practice setting. We analyzed the adverse events experienced in 27 hospitalized patients who had received AMR monotherapy by collecting data from the pharmaceutical management records. Neutropenia was the main hematological toxicity, and 77.8% of patients developed grade 3/4 neutropenia. Neutrophil counts reached the nadir in 9 to 21 (median 14) days and recovered to normal in 14 to 27 (median 20) days. Seven cases experienced febrile neutropenia without any serious sequelae. Grade 2 or worse non-hematological toxicities were fatigue, constipation, nausea, vomiting, anorexia, and pneumonitis. In comparison with the data of pre-marketing clinical trials, constipation was more commonly observed, while nausea/vomiting was less frequent probably due to appropriate preventive antiemetics. Based on these findings, we have created a novel drug information chart for patients and utilized it in pharmaceutical care in our hospital.

Topics: Aged; Aged, 80 and over; Anorexia; Anthracyclines; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Drug Administration Schedule; Fatigue; Female; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Nausea; Neutropenia; Vomiting, Anticipatory