A phase II study of amrubicin, a synthetic 9-aminoanthracycline, in patients with previously treated lung cancer

Kaira, Kyoichi; Sunaga, Noriaki; Tomizawa, Yoshio; Yanagitani, Noriko; Shimizu, Kimihiro; Imai, Hisao; Utsugi, Mitsuyoshi; Iwasaki, Yasuki; Iijima, Hironobu; Tsurumaki, Hiroaki; Yoshii, Akihiro; Fueki, Naoto; Hisada, Takeshi; Ishizuka, Tamotsu; Saito, Ryusei; Mori, Masatomo

doi:10.1016/j.lungcan.2009.09.012

Cited by 49 publications

(53 citation statements)

References 22 publications

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“…In AMR monotherapy, AMR is administered at a dose of 35–45 mg/m 2 /day on 3 consecutive days every 3–4 weeks. In phase II trials of second- or third-line AMR monotherapy for the treatment of SCLC, the response rates and the overall survival were 21–53% and 6–12 months, respectively [4,5,6,7,8,9,10,11]. In the treatment of NSCLC, the response rates of AMR monotherapy were 12–28% [11,12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Risk Factors for Predicting Severe Neutropenia Induced by Amrubicin in Patients with Advanced Lung Cancer

et al. 2012

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Background: Neutropenia is one of the most frequent and dose-limiting toxicities in amrubicin (AMR) therapy. However, the predictive factors for the development of severe neutropenia in AMR therapy remain unknown. Methods: The subjects were 61 advanced lung cancer patients treated with AMR monotherapy. All data were retrospectively collected from the electronic medical record system. A stepwise logistic regression analysis was performed to identify risk factors for grade 3–4 neutropenia. Results: Of a total 61 patients, 50 were male and 11 were female. The median dose of AMR was 35.0 mg/m². The incidence of grade 3–4 neutropenia during the first course was 62%. In multivariate analysis, female gender (OR = 6.68; 95% CI 1.01–134.15; p = 0.049), higher AMR doses (40 mg/m² or more) (OR = 5.98; 95% CI 1.77–23.74; p = 0.003), and lower hematocrit values (OR = 2.04 per 5% decrease; 95% CI 1.04–4.38; p = 0.036) were significantly associated with severe neutropenia induced by AMR. Conclusion: The present results suggest that female gender, higher doses of AMR, and lower baseline hematocrit values are predictive factors associated with severe neutropenia induced by AMR in patients with advanced lung cancer. Patients who have these predictive factors should be monitored carefully and considered for early granulocyte colony-stimulating factor support.

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Section: Introductionmentioning

confidence: 99%

Risk Factors for Predicting Severe Neutropenia Induced by Amrubicin in Patients with Advanced Lung Cancer

et al. 2012

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“…In addition, some authors have described positive effects and acceptable toxicity of amrubicin monotherapy in previously treated patients with NSCLC (3,5). Amrubicin as a single agent was approved at a dosage of 45 mg/m 2 /day in chemotherapy-naïve patients with lung cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Its antitumor effects are thought to be derived from a metabolic reduction in tumor cells and conversion to the active metabolic amrubicinol, which more potently inhibits cell growth by about 200-fold compared to the parent compound (1). Amrubicin has more potent antitumor effects in vivo, with less cardio-, hepato-and nephrotoxicity than other anthracycline antican-monotherapy in previously treated lung cancer patients has been determined, the dose of amrubicin in such patients must be reduced (3,(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Amrubicin Monotherapy for Elderly Patients with Previously Treated Lung Cancer

et al. 2010

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Objective The novel anthracycline agent amrubicin, has been approved in Japan to treat small and nonsmall cell lung cancers (SCLC and NSCLC). The present study evaluates the toxicity and effect of amrubicin especially in elderly patients with previously treated lung cancer. Patients and MethodsThis retrospective study analyzed data from 51 patients (<70 years of age, n=29; !70 years of age, n=22) with lung cancer (NSCLC, n=21; SCLC, n=30) who were treated with amrubicin at our hospital, between July 2003 and October 2009. All patients had recurrent or refractory lung cancer after one or more chemotherapy regimens. We compared the outcomes of patients younger and older than 70 years of age. Amrubicin (30-40 mg/m 2 /day) was infused depending on patient performance status and laboratory data over a period of 5 minutes on days 1-3, with courses repeated at intervals of at least 3 weeks. The dose was modified according to myelosuppression. Results The mean number of treatment cycles, mean dose and mean interval of amrubicin administration did not significantly differ between patients aged <70 and !70 years. The rate of hematological toxicities (! Grade 3) also did not significantly differ between the two age groups (leukopenia, 48.3% and 59.1% for age <70 and !70 years, p=0.573; neutropenia, 65.5% vs. 77.3%, p=0.536; anemia, 20.7% vs. 22.7%, p= 1.000; thrombocytopenia, 13.8% vs. 31.8%, p=0.173). The incidence of grade 2-4 non-hematological toxicities also did not significantly differ between the groups. The response rate of SCLC and disease control rate of NSCLC were similar in the younger and older groups. Conclusion Amrubicin monotherapy might be equally tolerated by elderly and younger patients. Further studies are needed to investigate the benefit of amrubicin monotherapy among elderly patients with previously treated lung cancer.

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“…Amrubicin and amrubicinol are topoisomerase II inhibitors, which have been demonstrated to exert antitumor activities in various human tumor xenograft models (7). The drug has been evaluated in a number of Japanese studies and reported to yield a response rate of 36-52% and a median survival time of 7-12 months when administered as a second-line treatment (8)(9)(10)(11)(12)(13). The results of previous studies have indicated that amrubicin is useful for the treatment of relapsed SCLC (8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Correlation between the efficacy of amrubicin and the previous chemotherapy regimen for relapsed small cell lung cancer

et al. 2017

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Abstract. Amrubicin has been demonstrated to be beneficial in the treatment of patients with relapsed small cell lung cancer (SCLC). The aim of the present study was to evaluate whether there is a significant difference in the efficacy of amrubicin between patients with relapsed SCLC who were previously treated with a platinum agent in combination with a topoisomerase I inhibitor, and those patients previously treated with a platinum agent in combination with a topoisomerase II inhibitor. The medical records of patients with SCLC, who were diagnosed as having relapsed following treatment with a platinum-based regimen and subsequently received amrubicin monotherapy, were retrospectively reviewed. Of a total of 48 patients with SCLC who were treated with amrubicin, the overall response rate, median progression-free survival (PFS) time and median survival time (MST) were determined to be 31.3%, 7.1 and 17.0 months, respectively. The response rate, PFS time and MST did not differ significantly between the patients treated previously with a platinum agent in combination with irinotecan, a topoisomerase I inhibitor, (36.4%, 5.7 and 11.4 months, respectively) and those treated previously with a platinum agent in combination with etoposide, a topoisomerase II inhibitor (30.0%, 4.7 and 14.8 months, respectively). The results indicate that amrubicin may be effective as a second-line chemotherapeutic agent for patients with SCLC, irrespective of which platinum agent and topoisomerase inhibitor-based chemotherapy regimen was previously administered. IntroductionSmall-cell lung cancer (SCLC) is the most aggressive type of lung cancer and has a poor prognosis (1). The standard therapy for extensive SCLC is chemotherapy with a platinum compound (carboplatin or cisplatin) administered in combination with etoposide, a topoisomerase II inhibitor (2). A Japanese phase III study [Japan Clinical Oncology Group (JCOG) 9511] investigated the clinical outcomes patients who were administered cisplatin and etoposide, compared with those who received cisplatin and irinotecan, a topoisomerase I inhibitor (3). Irrespective of the regimen selected, the majority of patients experience relapse or disease progression following an initial response to chemotherapy, and second-line therapy is subsequently required (4,5).Amrubicin is a synthetic 9-aminoanthracycline that is converted to its active metabolite, amrubicinol, through the reduction of its C-13 ketone group to a hydroxy group (6). Amrubicin and amrubicinol are topoisomerase II inhibitors, which have been demonstrated to exert antitumor activities in various human tumor xenograft models (7). The drug has been evaluated in a number of Japanese studies and reported to yield a response rate of 36-52% and a median survival time of 7-12 months when administered as a second-line treatment (8-13). The results of previous studies have indicated that amrubicin is useful for the treatment of relapsed SCLC (8-13).Few previous studies have evaluated the efficacy of amrubicin as a second-line treatmen...

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A phase II study of amrubicin, a synthetic 9-aminoanthracycline, in patients with previously treated lung cancer

Cited by 49 publications

References 22 publications

Risk Factors for Predicting Severe Neutropenia Induced by Amrubicin in Patients with Advanced Lung Cancer

Risk Factors for Predicting Severe Neutropenia Induced by Amrubicin in Patients with Advanced Lung Cancer

Amrubicin Monotherapy for Elderly Patients with Previously Treated Lung Cancer

Correlation between the efficacy of amrubicin and the previous chemotherapy regimen for relapsed small cell lung cancer

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