-
Expert Opinion on Drug Metabolism &... Feb 2009Although the advancement of the chemotherapy of non-small cell lung cancer and small cell lung cancer is remarkable in recent years, it is still unsatisfactory.... (Review)
Review
Although the advancement of the chemotherapy of non-small cell lung cancer and small cell lung cancer is remarkable in recent years, it is still unsatisfactory. Therefore, some new agents or a new treatment strategy for lung cancer is required. Amrubicin is a totally synthetic anthracycline anticancer drug that acts as a potent topoisomerase II inhibitor. Recently, amrubicin has been approved in Japan for the treatment of small- and non-small cell lung cancers and some clinical trials about amrubicin were conducted in Japan, and promising results have been reported for the treatment of small cell lung cancer in particular. The preclinical, pharmacology and clinical data of amrubicin for the treatment of advanced lung cancer are reviewed.
Topics: Animals; Anthracyclines; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Clinical Trials as Topic; Drug Approval; Drug Evaluation, Preclinical; Humans; Japan; Lung Neoplasms; Topoisomerase II Inhibitors
PubMed: 19239396
DOI: 10.1517/17425250802670508 -
Investigational New Drugs Oct 2007Amrubicin is a totally synthetic anthracycline anticancer drug and a potent topoisomerase II inhibitor. Recently, amrubicin was approved in Japan for the treatment of... (Review)
Review
Amrubicin is a totally synthetic anthracycline anticancer drug and a potent topoisomerase II inhibitor. Recently, amrubicin was approved in Japan for the treatment of small- and non-small-cell lung cancers (SCLC and NSCLC). Here, we review the efficacy and toxicities of amrubicin monotherapy and amrubicin in combination with cisplatin for extensive-disease SCLC (ED-SCLC), and of amrubicin monotherapy for advanced NSCLC, as observed in the clinical trials. Recommended dosage for previously untreated advanced NCSLC was 45 mg/m2/day by intravenous administration for 3 days. Dose-limiting toxicities were leucopenia, thrombocytopenia, and gastrointestinal disturbance. Response rate was 27.9% for advanced NSCLC, and 75.8% for ED-SCLC with a median survival time (MST) of 11.7 months. Recommended dosage of amrubicin was 40 mg/m2/day in combination with cisplatin at 60 mg/m2/day, with MST of 13.6 months and 1-year survival rate of 56.1%. In sensitive or refractory relapsed SCLC, response rate was 52 and 50%, progression-free survival was 4.2 and 2.6 months, overall survival was 11.6 and 10.3 months, and 1-year survival rate was 46 and 40%, respectively. These results are promising for the treatment of both NSCLC and SCLC. Further clinical trials will clarify the status of amrubicin in the treatment of lung cancer.
Topics: Anthracyclines; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Clinical Trials as Topic; Humans; Neoplasm Recurrence, Local
PubMed: 17628745
DOI: 10.1007/s10637-007-9069-0 -
Scientific Reports Jan 2016Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous... (Meta-Analysis)
Meta-Analysis Review
Currently, amrubicin is permitted for relapsed small-cell lung carcinoma (SCLC) only in Japan. The efficacy and adverse effects of amrubicin as reported by previous studies varied greatly. The inclusion criterion was a prospective study that was able to provide data for efficacy and safety by the AMR single agent regimen as second-line chemotherapy for a patient with SCLC. Binary data were meta-analyzed with the random-model generic inverse variance method. We included nine articles consisted of 803 patients. The pooled three-, six-, and nine-month progression-free survival were 63% (95% CI 57-69%, I(2) = 53%), 28% (95% CI 21-35%, I(2) = 71%), and 10% (95% CI 6-14%, I(2) = 41%), respectively. The pooled six-, 12-, and 18-month overall survival were 69% (95% CI 61-78%, I(2) = 83%), 36% (95% CI 28-44%, I(2) = 80%), and 15% (95% CI 8-21%, I(2) = 81%), respectively. Amrubicin seemed much more beneficial for Japanese patients. However, compared to the efficacy of topotecan presented in a previous meta-analysis, amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American. Adverse effects by amrubicin were almost exclusively observed to be hematological. Notably, grade III/IV neutropenia incidence was 70% and febrile neutropenia incidence was 12%.
Topics: Anthracyclines; Antineoplastic Agents; Asian People; Humans; Japan; Lung Neoplasms; Neutropenia; Recurrence; Small Cell Lung Carcinoma; Survival Analysis; Topotecan; Treatment Outcome; White People
PubMed: 26750506
DOI: 10.1038/srep18999 -
Journal of Thoracic Oncology : Official... Feb 2007Amrubicin is a synthetic 9-aminoanthracycline that has significant antitumor activity in Japanese patients with extensive stage small cell lung cancer (SCLC). Clinical... (Review)
Review
Amrubicin is a synthetic 9-aminoanthracycline that has significant antitumor activity in Japanese patients with extensive stage small cell lung cancer (SCLC). Clinical trials ongoing in the United States and Europe will determine whether amrubicin will be effective in other ethnic groups (whites) or whether this will be an example of geographic and/or genetic variation. Genetic polymorphisms in the UGT1A1 gene have been identified as one of the causes of the increased diarrhea seen in white patients treated with irinotecan when compared with Japanese patients. Nicotinamide adenine dinucleotide phosphate, reduced form-quinone oxidoreductase (NQ01) is an enzyme that participates in the metabolism of amrubicin and polymorphisms of the enzyme, known to occur in the Asian population, might explain the effectiveness of the drug in Japanese patients with small cell lung cancer. Studies to evaluate the drug in US and European patients with extensive stage small cell lung cancer are ongoing. Levels of NQ01 will also be determined in these studies.
Topics: Anthracyclines; Antineoplastic Agents; Carcinoma, Small Cell; Cisplatin; Europe; Humans; Japan; Lung Neoplasms; Topotecan; United States
PubMed: 17410034
DOI: 10.1097/jto.0b013e31802f1cd9 -
Nihon Rinsho. Japanese Journal of... May 2002
Review
Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Evaluation, Preclinical; Humans; Lung Neoplasms; Treatment Outcome
PubMed: 12101692
DOI: No ID Found -
Mayo Clinic Proceedings Aug 2019Small-cell lung cancer (SCLC) is an aggressive disease with distinct pathological, clinical, and molecular characteristics from non-small-cell lung cancer. SCLC has high... (Review)
Review
Small-cell lung cancer (SCLC) is an aggressive disease with distinct pathological, clinical, and molecular characteristics from non-small-cell lung cancer. SCLC has high metastatic potential, resulting in a clinically poor prognosis. Early concurrent chemo-radiation is the standard of care for limited-stage SCLC (LS-SCLC). Prophylactic cranial irradiation (PCI) is recommended for patients with LS-SCLC without progression of disease after initial therapy. A combination of etoposide and cisplatin or carboplatin remains the mainstay of first-line treatment for ES-SCLC, with the addition of atezolizumab, now becoming standard. Most SCLCs initially respond to therapy but almost invariably recur. Topotecan and amrubicin (in Japan) remain the primary chemotherapy options for relapsed SCLC. Immunotherapy, including nivolumab with or without ipilimumab, is now available for refractory disease. In general, the poor prognosis of SCLC has not improved significantly for more than 3 decades. Recently, next-generation molecular profiling studies have identified new therapeutic targets for SCLC. A variety of proapoptotic agents, compounds capitalizing on DNA-repair defects, immunotherapy agents, and antibody-drug conjugates are being evaluated in SCLC, with a number of them showing early promise.
Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Disease Management; Disease-Free Survival; Female; Humans; Immunotherapy; Japan; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Prognosis; Risk Assessment; Survival Analysis
PubMed: 31378235
DOI: 10.1016/j.mayocp.2019.01.034 -
Drug Design, Development and Therapy 2013Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer characterized by early metastasis and high mortality. In recent years, monotherapy and... (Review)
Review
Small-cell lung cancer (SCLC) is the most aggressive form of lung cancer characterized by early metastasis and high mortality. In recent years, monotherapy and combination therapy of amrubicin with cisplatin or carboplatin has been actively studied and shown promise for the treatment of extensive disease SCLC (ED-SCLC). In this article, we summarize clinical trials of both monotherapy and combination therapy with amrubicin conducted in Japan, the USA, and the European Union. The results suggest that the clinical outcome of amrubicin therapy may be associated with genetic variations in patients. Further study of combination regimens in patients of different ethnicities is warranted.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Clinical Trials as Topic; Humans; Lung Neoplasms; Small Cell Lung Carcinoma
PubMed: 23946645
DOI: 10.2147/DDDT.S41910 -
Recent Patents on Anti-cancer Drug... Nov 2009Amrubicin is a synthetic anthracyclin analogue that has significant activity in Japanese patients with extensive stage small cell lung cancer (ES-SCLC). There has not... (Review)
Review
Amrubicin is a synthetic anthracyclin analogue that has significant activity in Japanese patients with extensive stage small cell lung cancer (ES-SCLC). There has not been significant advances made in the treatment of this disease in last several years and new therapies are desperately needed to change the natural history of this disease. Preliminary data has shown that amrubicin possesses anti-tumor activity in patients with extensive stage small cell lung cancer in the western population. Clinical trials are on going to evaluate this agent further in Europe and U.S. If effective, it may be an invaluable addition into the current armamentarium to treat this deadly disease. The review includes patent coverage on the treatment of small cell lung cancer.
Topics: Anthracyclines; Antineoplastic Agents; Clinical Trials as Topic; Humans; Lung Neoplasms; Small Cell Lung Carcinoma
PubMed: 19538159
DOI: 10.2174/157489209789206850 -
Annals of Oncology : Official Journal... May 2021Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with relapsed small-cell lung cancer (SCLC) have few treatment options and dismal survival. Phase I/II data show activity of nivolumab in previously treated SCLC.
PATIENTS AND METHODS
CheckMate 331 is a randomized, open-label, phase III trial of nivolumab versus standard chemotherapy in relapsed SCLC. Patients with relapse after first-line, platinum-based chemotherapy were randomized 1 : 1 to nivolumab 240 mg every 2 weeks or chemotherapy (topotecan or amrubicin) until progression or unacceptable toxicity. Primary endpoint was overall survival (OS).
RESULTS
Overall, 284 patients were randomized to nivolumab and 285 to chemotherapy. Minimum follow-up was 15.8 months. No significant improvement in OS was seen with nivolumab versus chemotherapy [median OS, 7.5 versus 8.4 months; hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.72-1.04; P = 0.11]. A survival benefit with nivolumab was suggested in patients with baseline lactate dehydrogenase ≤ upper limit of normal and in those without baseline liver metastases. OS (nivolumab versus chemotherapy) was similar in patients with programmed death-ligand 1 combined positive score ≥1% versus <1%. Median progression-free survival was 1.4 versus 3.8 months (HR, 1.41; 95% CI, 1.18-1.69). Objective response rate was 13.7% versus 16.5% (odds ratio, 0.80; 95% CI, 0.50-1.27); median duration of response was 8.3 versus 4.5 months. Rates of grade 3 or 4 treatment-related adverse events were 13.8% versus 73.2%.
CONCLUSION
Nivolumab did not improve survival versus chemotherapy in relapsed SCLC. No new safety signals were seen. In exploratory analyses, select baseline characteristics were associated with improved OS for nivolumab.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Lung Neoplasms; Neoplasm Recurrence, Local; Nivolumab; Progression-Free Survival; Small Cell Lung Carcinoma
PubMed: 33539946
DOI: 10.1016/j.annonc.2021.01.071 -
Thoracic Cancer Jul 2020The aim of this study was to assess the efficacy and safety of amrubicin for previously treated malignant pleural mesothelioma.
BACKGROUND
The aim of this study was to assess the efficacy and safety of amrubicin for previously treated malignant pleural mesothelioma.
METHODS
The eligibility criteria were: previously treated unresectable malignant pleural mesothelioma; performance status 0-1; age ≤ 75; adequate hematological, hepatic, and renal function. The patients were injected with 35 mg/m amrubicin on days one, two, and three every 3-4 weeks. The planned number of patients was 32.
RESULTS
The study was terminated due to delay in enrollment and 10 patients were subsequently enrolled (nine males and one female; median age 67 [range 49-73]), of which four had epithelioid tumors, three had sarcomatoid tumors and three had biphasic tumors, respectively. According to the International Mesothelioma Interest Group (IMIG), one, four, and four patients had stage II, III, and IV, respectively, and one had postoperative recurrence. There was one (10%) partial response, four (40%) had stable disease, and five (50%) patients exhibited disease progression. The overall response and disease control rates were 10% (95% CI: 0.3-44.5%) and 60% (95% CI: 26.2-87.8%), respectively. The median progression-free survival time was 1.6 months. The median overall survival time was 6.6 months, and the one-, two-, and three-year survival rates were 23%, 23%, and 0%, respectively. The observed grade 3 or 4 toxicities included neutropenia in six (60%) patients; leukopenia in five (50%) patients; and febrile neutropenia, thrombocytopenia, anemia, and pneumonia in one (10%) patient each.
CONCLUSIONS
There was not enough data to evaluate the efficacy because the study was terminated early. However, amrubicin showed limited activity and acceptable toxicities when used in previously treated malignant pleural mesothelioma patients.
Topics: Aged; Anthracyclines; Antineoplastic Agents; Female; Follow-Up Studies; Humans; Male; Mesothelioma, Malignant; Middle Aged; Neoplasm Recurrence, Local; Pleural Neoplasms; Prognosis; Salvage Therapy; Survival Rate
PubMed: 32462731
DOI: 10.1111/1759-7714.13490