amrubicin and Liver-Neoplasms

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

Combination chemotherapy of irinotecan, a topoisomerase I inhibitor, and cisplatin is a standard treatment in patients with extensive-stage small cell lung cancer (SCLC). Amrubicin, a novel 9-aminoanthracycline, inhibits topoisomerase II. We investigated a sequential triplet chemotherapy consisting of irinotecan and cisplatin followed by amrubicin in patients with extensive-stage SCLC.. Eligible patients were aged 20 to 70 years and had Eastern Cooperative Oncology Group performance status of 0 or 1, measurable lesions, and adequate organ functions. Chemotherapy consisted of irinotecan 60 mg/m on days 1 and 8 plus cisplatin 60 mg/m on day 1 every 3 weeks for three cycles and then amrubicin 40 mg/m alone on days 1 to 3 every 3 weeks for three cycles.. From September 2004 to September 2006, 45 patients were enrolled, 43 were evaluable for response and survival, and 44 were evaluable for toxicity. Twenty-eight patients (64%) completed the full planned chemotherapy. One patient achieved complete response and 33 had partial response for an overall response rate of 79%. Median progression-free survival was 6.5 months. Median overall survival was 15.4 months. Major toxicity was myelosuppression. Grade 3 or 4 neutropenia, anemia, thrombocytopenia, and febrile neutropenia occurred in 57%, 7%, 0%, and 7% of patients during irinotecan/cisplatin cycles and in 91%, 27%, 9%, and 15% of patients during amrubicin cycles, respectively.. The sequential triplet chemotherapy, irinotecan and cisplatin followed by amrubicin, is an effective and well-tolerated treatment in patients with extensive-stage SCLC. Further investigation of this treatment is warranted.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Camptothecin; Cisplatin; Female; Humans; Irinotecan; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Small Cell Lung Carcinoma; Survival Rate; Treatment Outcome; Young Adult

Topics: Anthracyclines; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Benzodiazepinones; Carboplatin; Clinical Decision-Making; Disease Progression; Etoposide; Humans; Immunoconjugates; Irinotecan; Liver Neoplasms; Lung Neoplasms; Molecular Targeted Therapy; Neoplasm Recurrence, Local; Nivolumab; Paclitaxel; Piperazines; Pyrimidines; Salvage Therapy; Small Cell Lung Carcinoma; Temozolomide; Thiourea; Topotecan

We reported a case of small cell lung cancer treated with amrubicin while receiving hemodialysis. An 83-year-old man with chronic renal failure being treated by hemodialysis was admitted because of a left hilar mass. Small cell lung cancer with liver metastasis (cT2NOM1) was diagnosed. Two courses of chemotherapy with amrubicin resulted in partial response. Toxicity was relatively mild. We measured blood concentration of amrubicin during the first course of chemotherapy. There was no significant difference in blood cell and plasma concentration of amrubicin hydrochloride and amrubicinol between days when he received hemodialysis and when he did not receive hemodialysis. Thus, we considered that amrubicin hydrochloride may be a good candidate for the treatment of small cell lung cancer patients with chronic renal failure under hemodialysis.

Topics: Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Carcinoma, Small Cell; Drug Administration Schedule; Humans; Kidney Failure, Chronic; Liver Neoplasms; Lung Neoplasms; Male; Renal Dialysis