Phase II study of amrubicin, 9-amino-anthracycline, in patients with advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group (WJTOG) study

Takeda, Koji; Takifuji, Nobuhide; Negoro, Shunichi; Furuse, Kiyoyuki; Nakamura, Shinichiro; Takada, Yoshiki; Hoso, Takanobu; Hayasaka, Shôzô; Nakano, Takashi; Araki, Jun; Senba, Hiroshi; Iwami, Fumiyuki; Yamaji, Yutaka; Fukuoka, Masahiro; Ikegami, Harumichi

doi:10.1007/s10637-007-9039-6

Cited by 25 publications

(20 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hematologic toxicity was found to be the principal toxicity of amrubicin monotherapy in previous phase II studies [14,15,16]. Likewise, the major adverse events in our study were hematologic toxicity, especially neutropenia and leukopenia.…”

Section: Discussionsupporting

confidence: 74%

“…Likewise, the major adverse events in our study were hematologic toxicity, especially neutropenia and leukopenia. Nevertheless, the toxicities were evaluated under third-line or later-line conditions, and no increases in Grade 3 or 4 hematologic toxicity were observed in comparison with the results reported in the above-mentioned phase II studies [14,15,16]. The incidences of severe neutropenia and leukopenia in our study were lower in the group of patients who received the 35 mg/m 2 dose than in the group treated with 40 mg/m 2 , and the clinical response of the 35 mg/m 2 group patients was not inferior to that of the 40 mg/m 2 group.…”

Section: Discussionmentioning

confidence: 99%

“…Two phase II studies of amrubicin in patients with previously untreated advanced NSCLC demonstrated in succession an overall response rate of 27.9 and 18.3%, respectively, and a median survival time (MST) of 9.8 months and 8.2 months, respectively [14,15]. This showed that amrubicin is equivalent to newer agents such as taxanes, gemcitabine, vinorelbine and pemetrexed in terms of single-agent activity against NSCLC.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of Amrubicin as a Third or Later Line of Chemotherapy for Advanced Non-Small Cell Lung Cancer

Igawa¹,

Sasaki²,

Ishihara³

et al. 2013

Chemotherapy

View full text Add to dashboard Cite

Background: Currently, there are no standard cytotoxic treatments for non-small-cell lung cancer (NSCLC) patients beyond third-line therapy. The purpose of this study was to evaluate the efficacy of amrubicin monotherapy as a salvage treatment in heavily pretreated NSCLC patients. Methods: The records of NSCLC patients who received amrubicin monotherapy as a third or later line of chemotherapy at a Kitasato University Hospital between January 2009 and December 2012 were retrospectively reviewed. Amrubicin was administered to patients by intravenous injection at a dose of 35 or 40 mg/m² daily on 3 consecutive days, and cycles were repeated at 3-week intervals. Results: There were 36 patients who met the inclusion criteria. Their median number of prior chemotherapy treatments was 4 (range 2-7), and the median number of chemotherapy cycles per patient was 4 (range 1-9). Grade 3 or 4 hematologic toxicities included neutropenia (61.1%), leukopenia (58.3%), thrombocytopenia (22.2%) and anemia (11.1%). Febrile neutropenia occurred in 8 patients (22.2%). Nonhematologic toxicities were mild. The overall response rate, median progression-free survival time and median survival time were 8.3%, 1.7 months, and 6.3 months, respectively. Progression-free survival time was the same, i.e. 1.7 months in both groups i.e. the 35- and the 40-mg/m²-dose groups. Conclusion: Amrubicin exhibits modest activity and acceptable toxicity when used as a third or later line of chemotherapy for advanced NSCLC.

show abstract

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of Amrubicin as a Third or Later Line of Chemotherapy for Advanced Non-Small Cell Lung Cancer

Igawa¹,

Sasaki²,

Ishihara³

et al. 2013

Chemotherapy

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…Amrubicin and amrubicinol are inhibitors of DNA topoisomerase II, developing their cytotoxic effects by stabilizing a topoisomerase II-mediated cleavable complex. The two clinical studies of amrubicin alone for patients with previously untreated NSCLC have shown objective response rates of 28 and 18%, and median survival of 9.8 and 8.2 months [14,15]. The phase II trial in combination with platinum for previously untreated patients of extensive-stage small cell lung cancer demonstrated a favorable outcome (response rate 87.8%, MST 13.6 months) [16], but no trial of the combination with cisplatin for NSCLC has been performed.…”

Section: Introductionmentioning

confidence: 99%

Phase I/II Study of Amrubicin and Nedaplatin in Patients with Untreated, Advanced, Non-Small Cell Lung Cancer

et al. 2014

View full text Add to dashboard Cite

A phase I/II study of combination chemotherapy with amrubicin and nedaplatin for patients with untreated, advanced, non-small cell lung cancer (NSCLC) was conducted. Amrubicin was given on days 1-3, with nedaplatin given on day 1. The treatment was repeated every 3 weeks. In the phase I trial, the initial amrubicin dose of 25 mg/m² was escalated in 5-mg/m² increments until the maximum tolerated dose was reached, with the dose of nedaplatin fixed at 100 mg/m². In the phase II trial, the primary endpoint was the overall response rate (ORR), assuming 20% for a standard therapy and 40% for a target therapy (α = 0.05 and β = 0.20), and the estimated required total number of patients was 35. In the phase I study, nedaplatin 100 mg/m² and amrubicin 25 mg/m² was recommended. In the phase II study, 17 out of 35 patients achieved a partial response, and the ORR was 48.6%. Grade 3/4 neutropenia, grade 3 anemia and grade 3/4 thrombocytopenia occurred in 62.9, 11.4 and 11.4% of cycles, respectively. Febrile neutropenia occurred in 5 cycles (3.9%) and all cases were manageable. The recommended dose of this combination is well tolerated and effective in patients with advanced NSCLC.

show abstract

Phase II study of amrubicin, 9-amino-anthracycline, in patients with advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group (WJTOG) study

Abstract: Amrubicin was an active, well-tolerated agent in the treatment of NSCLC.

Cited by 25 publications

References 16 publications

Evaluation of Amrubicin as a Third or Later Line of Chemotherapy for Advanced Non-Small Cell Lung Cancer

Evaluation of Amrubicin as a Third or Later Line of Chemotherapy for Advanced Non-Small Cell Lung Cancer

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

Phase I/II Study of Amrubicin and Nedaplatin in Patients with Untreated, Advanced, Non-Small Cell Lung Cancer

Contact Info

Product

Resources

About