Safety Of Amrubicin Research Articles

1535P Efficacy and safety of amrubicin after treatment with immune checkpoint inhibitor combined with chemotherapy in extensive-stage small cell carcinoma: MiSSION1

Previous studies have shown that adding immune checkpoint inhibitor (ICI) to chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) is effective and is currently the first-line treatment. However, there is no evidence whether it is effective as a second-line treatment after first-line chemotherapy and ICI combination therapy. Amrubicin is recommended as a second-line treatment for ES-SCLC in the guideline, and it is frequently used in Japan. Here, we report a retrospective study on the efficacy and safety of amrubicin as a second-line treatment for ES-SCLC after ICI therapy.

Efficacy and Safety of Amrubicin in Small Cell Carcinoma Previously Treated with Immune Checkpoint Inhibitors and Chemotherapy.

Simple SummaryTherapeutic efficacy of chemotherapy combined with immune checkpoint inhibitors as first-line therapy has been previously demonstrated in extensive-stage small cell lung cancer. However, there are no reports of any cytotoxic drug that is effective as second-line therapy in extensive-stage small cell lung cancer patients previously treated with chemotherapy and immune checkpoint inhibitors as a first-line treatment. In the present study, we retrospectively evaluated patients with extensive-stage small cell lung cancer to clarify whether the previous treatment with chemotherapy and immune checkpoint inhibitors impacts the efficacy and safety of amrubicin as a second-line treatment. This study shows that the efficacy and safety of amrubicin in extensive-stage small cell lung cancer remains unchanged irrespective of previous treatment with chemotherapy and immune checkpoint inhibitors.Adding an immune checkpoint inhibitor to chemotherapy to treat extensive-stage small cell lung cancer is effective. However, there are no reports of an effective second-line treatment in patients previously treated with chemotherapy and immune checkpoint inhibitors as a first-line treatment. Here, we assessed the efficacy and safety of amrubicin as a second-line treatment for extensive-stage small cell lung cancer after chemotherapy and immune checkpoint inhibitor combination therapy. The study enrolled 150 patients with extensive-stage small cell lung cancer. The efficacy and the incidence of adverse events were compared between patients previously treated with immune checkpoint inhibitors and patients without previous immune checkpoint inhibitor treatment. One hundred and twenty-three patients were eligible. There was no difference in objective response rate, time-to-treatment failure, progression-free survival, and overall survival between both groups. The incidence of adverse events was similar in both treatment groups. Pretreatment with immune checkpoint inhibitors was not associated with an increase in amrubicin-related adverse events. This study shows that the efficacy of amrubicin in extensive-stage small cell lung cancer remains unchanged irrespective of previous treatment with immune checkpoint inhibitors. Amrubicin-related adverse events did not increase in patients previously treated with immune checkpoint inhibitors.

The safety and efficacy of amrubicin in the treatment of previously untreated extensive-disease small-cell lung cancer: a meta-analysis.

Background: Extensive-disease small-cell lung cancer (ED-SCLC) has been known to be rapid progression and relapse, despite highly sensitive to chemotherapy. Amrubicin (AMR), a third-generation synthetic anthracycline, was accepted as a feasible alternative compared with the standard first-line chemotherapy for previously untreated ED-SCLC. While, the efficacies of these amrubicin-based regimens are unsatisfactory.Aim: Our meta-analysis was performed to assess the efficacy and toxicity of first-line therapy comparing AMR and chemotherapy in patients with ED-SCLC.Methods: Electronic databases were searched for eligible trials updated on November 2018. Randomized-controlled trials assessing the efficacy and safety of AMR in ED-SCLC were included, of which the interested results were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs).Results: A total of 6 randomized controlled trials were included in this analysis. There are no significant differences in OS (OR=1.03, 95% CI=0.66–1.60, P=0.91), PFS (OR=1.2, 95% CI=10.77–1.88, P=0.41) or ORR (OR=1.31, 95% CI=0.90–1.92, P=0.16) with AMR (OR=0.90, 95% CI=0.76–1.05, P=0.17). The most common treatment-related AEs in the AMR group are leukopenia (OR=3.13, 95% CI=1.22–7.99, P=0.02) and neutropenia (OR=3.25, 95% CI=1.38–7.65, P=0.007). Fatigue, anemia, nausea, vomiting, diarrhea the difference between the two groups had no statistical significance.Conclusion: The results of our analysis indicated that AMR therapy demonstrated non-inferiority to the standard first-line chemotherapy for previously untreated ED-SCLC. Whether it can be accepted as an alternative regimen to the standard first-line chemotherapy is still warranted.

Efficacy and Safety of Amrubicin in Non-Small-Cell Lung Cancer Patients Beyond Third-Line Therapy

Background: 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 and safety of amrubicin in pretreated NSCLC patients. Methods: The records of NSCLC patients who received amrubicin monotherapy as a third or later line of chemotherapy at Shizuoka General Hospital between April 2007 and March 2015 were retrospectively reviewed. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 3.0. Results: Overall, 69 patients were enrolled in this study; 16 patients were female and the median age was 67 years. The median number of treatment cycles was 3. The response rate was 7.2%, and the disease control rate was 63.8%. The median progression-free survival was 2.8 months. The median overall survival was 7.7 months. Hematological toxicities of ≥ grade 3 included leukopenia (59.4%) and neutropenia (62.3%). Non-hematological toxicities of ≥ grade 2 included anorexia (27.5%) and fatigue (24.6%). Conclusion: Although hematological toxicities were severe, these results suggested that amrubicin in NSCLC patients beyond third-line therapy shows sufficient clinical benefit.

184P: The efficacy and safety of amrubicin in non-small-cell lung cancer patients beyond third-line therapy

184P: The efficacy and safety of amrubicin in non-small-cell lung cancer patients beyond third-line therapy

3080 Polled analysis of nivolumab for the treatment of advanced non-small cell lung cancer and the role of PD-L1 as a biomarker

the combination of amrubicin and topoisomerase II inhibitor irinotecan has yet to be examined in randomized clinical trials. We conducted a randomize phase II study to evaluate the efficacy and safety of amrubicin plus irinotecan (AI) compared with cisplatin and irinotecan (CI) in chemonaive patients with extensive-disease (ED) SCLC. Material and Methods: Eligibility criteria included ECOG PS 0−2, age 20 or older, pathologically proven SCLC, ED (Limited disease (LD) with pleural effusion was also eligible), adequate organ function, and written informed consent. Patients were randomized 1:1 to receive either AI (amrubicin 90mg/m on day1 and irinotecan 50mg/m on days 1 and 8 of a 21-day cycle) or CI (cisplatin 60mg/m on day1 and irinotecan 60mg/m on days 1, 8 and 15 of a 28-day cycle). The AI regimen was based on the recommended dose of our previous phase I trial JMTO LC 03−03 (Kawahara M, et al. J Thorac Oncol 2011). The primary endpoint was overall survival (1-year survival rate). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety profile. Stratification factors are PS (0−1 or 2), LDH value (within normal limit or not), institution, and clinical stage (ED or LD with pleural effusion). Results: A total of 100 patients were randomly assigned to AI (n = 50) and to CI (n = 50). One patient was ineligible and excluded from analysis. One-year survival rate was 68.0% (95% confidence interval: 56.2–82.2%) for AI and 62.8% (50.5–78.0%) for CI (one-sided p = 0.29). The stratified log-rank test of two curves comparison showed p = 0.11. Median survival time was 14.7 months for AI and 14.2 months for CI with a hazard ratio (HR) of 0.69. Median PFS was 4.2 months for AI and 5.4 months for CI (stratified log-rank test, p = 0.91). ORR was 70.0% (55.4–82.1%) for AI and 55.1% (40.2–69.3%) for CI (Fisher exact test, p = 0.15). There was no significant difference in hematological toxicity, whereas rates of vomiting, loss of appetite, diarrhea, and elevated serum creatinine are more frequent in CI. Interstitial lung disease (Grade 2 or 3) developed in 5 patients in AI and in 1 patient in CI. There was no treatment-related death. Conclusions: Although the study did not meet its primary endpoint, the combination of amrubicin plus irinotecan showed similar efficacy to that of cisplatin plus irinotecan in chemo-naive patients with ED SCLC. Conflict of interest: Corporate-sponsored Research: Yakult Pharmaceutical Industry.

Amrubicin Monotherapy in Patients with Platinum-Refractory Metastatic Neuroendocrine Carcinoma and Mixed Adenoneuroendocrine Carcinoma of the Gastrointestinal Tract

ABSTRACT Aim: We conducted a retrospective anaysis to investigate the efficacy and safety of Amrubicin (AMR) in patients with platinum-refractory metastatic neuroendocrine carcinoma and mixed neuroendocrine carcinoma of the gastrointestinal tract (GIT-NEC/MANEC). Methods: Patients with platinum-refractory extensive disease received AMR in the National Cancer Center Hospital between February 2004 and July 2012. AMR was administered 30-45 mg/m2 on days 1-3, and repeated every 3-4 weeks. The overall response rate (RR) was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, progression-free survival (PFS), overall survival (OS) were estimated by the Kaplan-Meier method, and adverse events based on Common Terminology Critera for Adverse Events (CTCAE) version 4.0. Results: Twenty-one patients received AMR. After a median eight-month follow-up, RR for 18 patients was 22.2% (95% CI, 3.0-41.4), median PFS was 3.7 months (2.6-4.8), and median OS was 7.8 months (7.2-8.4). Grade 3/4 neutropenia occurred in 52.4% of patients, and febrile neutropenia in 14.3%. Other non-hematologic toxicities were mild and no treatment-related deaths were observed. Conclusions: AMR displays tolerable toxicity and may be feasible and effective treatment of platinum-refractory GIT-NEC/MANEC patients. Further prospective evaluation of AMR for GIT-NEC/MANEC is warranted. Disclosure: All authors have declared no conflicts of interest.

A single-arm confirmatory study of amrubicin therapy in patients with refractory small-cell lung cancer: Japan Clinical Oncology Group Study (JCOG0901)

ObjectivesWe conducted an open-label, multicenter, single-arm study to confirm the efficacy and safety of amrubicin (AMR), a topoisomerase II inhibitor, for treating refractory small-cell lung cancer (SCLC). Patients and methodsPatients with chemotherapy-refractory SCLC received 40mg/m2 AMR for 3 consecutive days, every 21 days. The primary endpoint was the overall response rate (ORR) and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. ResultsBetween November 2009 and February 2011, 82 patients were enrolled. Each patient received a median of four treatment cycles (range, 1–22 cycles). ORR was 32.9% [P<0.0001 by the exact binomial test for the null hypothesis that ORR≤10%; 95% confidence interval (CI), 22.9–44.2%]. The median PFS and OS periods were 3.5 months (95% CI, 3.0–4.3 months) and 8.9 months (95% CI, 7.6–11.3 months), respectively. Significant differences in ORR (21.4% v 45.0%; P=0.034), PFS (median, 2.9 v 5.1 months; P=0.0009), and OS (median, 7.9 v 13.1 months; P=0.0128) were observed between patients previously treated with etoposide and others. Neutropenia was the most common grade 3 or 4 adverse events (93.9%), and febrile neutropenia developed in 26.8% patients. No treatment-related death occurred. ConclusionsAMR monotherapy can be considered an effective and safe treatment option for refractory SCLC. Previous chemotherapy with etoposide may influence AMR efficacy.

A Randomized Phase III Study of Single-Agent Amrubicin Vs. Carboplatin/Etoposide in Elderly Patients With Extensive-Disease Small-Cell Lung Cancer

IntroductionThe efficacy and safety of amrubicin, a third-generation synthetic anthracycline, were evaluated by comparison with carboplatin/etoposide combination therapy in elderly Japanese patients with extensive-disease small-cell lung cancer (ED-SCLC). Patients and MethodsEligibility included histologically or cytologically proven SCLC, no previous systemic chemotherapy, performance status of 0 to 2, and age ≥ 70 years. Patients received amrubicin (70-74 years old, 40-45 mg/m2; ≥ 75 years old, 40 mg/m2) intravenously on days 1 to 3 every 3 weeks for 4 to 6 cycles or carboplatin (area under the curve of 5 intravenously on day 1) and etoposide (80 mg/m2 intravenously on days 1 to 3) every 3 weeks for 4 to 6 cycles. ResultsThe target number of patients was 130 with 65 in each arm. However, the study was terminated early owing to 3 treatment-related deaths in the amrubicin arm, and only 62 patients (median age, 76 years; range, 70-88 years) were enrolled. The characteristics of the patients in the amrubicin and carboplatin/etoposide arms did not differ significantly. Overall survival, time to progression, and objective response rate were 10.9 vs. 11.3 months (P = .7353), 4.7 vs. 4.4 months, and 74.2% (23 of 31) vs. 60.0% (18 of 30), respectively, and quality of life showed no significant difference between the 2 arms. Higher incidences of febrile neutropenia and interstitial lung disease of grade 3 or worse occurred with amrubicin (34.4% vs. 3.3% and 12.5% vs. 0%, respectively). ConclusionThese results indicate that amrubicin monotherapy at 40 to 45 mg/m2 is toxic and intolerable in elderly Japanese patients with ED-SCLC.

1519PD - Phase II Study of Amrubicin in Patients with Refractory or Resistant Relapsed Small-Cell Lung Cancer: Japan Clinical Oncology Group Study (JCOG0901)

ABSTRACT Background Standard therapy for refractory or resistant relapsed small-cell lung cancer (SCLC) has not yet been established. We conducted an open-label, multicenter, non-randomized phase II study to confirm the efficacy and safety of amrubicin, a topoisomerase inhibitor, in the treatment of refractory or resistant SCLC. Material and methods Patients with SCLC that is refractory or relapsed within 90 days of completing previous treatment received amrubicin at a dose of 40 mg/m2 for 3 consecutive days, every 21 days.The study treatment was repeated until disease progression or intolerable toxicity. The primary end point was overall response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival (OS), and safety. Planned sample size was 80 patients to achieve power of at least 80% with one-sided alpha of 0.05, and expected and threshold value for primary endpoint as 20% and 10%. All patients were followed-up until one year after the last patient enrollment. Results Between November 2009 and February 2011, 82 patients were enrolled from 25 institutions. The median number of treatment cycles was four (range, one to 22 cycles).The ORR was 32.9% (p Conclusions Amrubicin demonstrated the favorable tumor response and survival with acceptable toxicity. Single-agent amrubicin could be considered as a standard regimen in the treatment of refractory or resistant relapsed SCLC. Disclosure All authors have declared no conflicts of interest.

1358 - Outcomes for Elderly, Advanced–Stage Non-Small Cell Lung Cancer (NSCLC) Patients Treated with Amrubicin (AMR) as Third-Line or Fourth-Line Chemotherapy: Analysis of Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0901

ABSTRACT Background HOT0901 trial evaluated the efficacy and safety of AMR, third-generation synthetic anthracycline agent, for NSCLC patients as third-line or fourth-line chemotherapy. We conducted a subset analysis of HOT0901 to determine the outcome for elderly patients. Methods Eligible patients had a performance status 0 to 2, failure of second-line or third-line chemotherapy, and adequate organ function. Patients received AMR 35 mg/m2 intravenously on days 1-3 every 3 weeks. The primary endpoint was disease control rate (DCR: CR + PR + SD). Secondary endpoints were overall survival (OS), progression-free survival (PFS), response rate (CR + PR), and toxicity profile. Elderly patients were defined as those at least 70 years of age at the time of enrollment. The efficacy and safety data for AMR therapy was compared between the elderly and younger patients ( Results There were 14 elderly and 27 younger patients in this study. Elderly patients accounted for 34% of the study cohort. Clinical characteristics such as PS or histologic subtypes were similar between the groups. The median number of treatment cycles was 3 in elderly and 2 in younger patients. The overall response rate and DCR were 14.3% and 71.4% in elderly patients and 7.4% and 55.5% in younger patients, respectively (p = 0.42 and 0.26). Median PFS was 3.6 and 2.4 months (p = 0.70), whereas median survival time was 11.3 and 13.9 months (p = 0.67) in elderly and younger patients. The most common grade 3/4 toxicity was neutropenia (64.3 vs. 70.4%); overall, there was no major difference in the incidence of hematological and nonhematological toxicities between the groups. No treatment-related death was observed in this study. Conclusion Third-line or fourth-line AMR yielded the similar efficacy and toxicity profiles between elderly and younger NSCLC patients. Data from this post-hoc analysis encourage prospective evaluation of potential benefit of AMR in elderly NSCLC patients. Disclosure All authors have declared no conflicts of interest.

Efficacy and safety of amrubicin in patients with advanced or recurrent thymoma.

e17513 Background: Thymoma is rare thoracic tumor, which is chemoresponsive with anthracycline or cisplatin-containing regimen in advanced or recurrent setting. Amrubicin is a novel anthracycline agent that is well known to exert significant activity against small-cell lung cancer. The purpose of this study was to determine the efficacy and safety of amrubicin in patients with advanced or recurrent thymoma. Methods: We reviewed 11 consecutive patients with advanced or recurrent thymoma treated with single-agent amrubicin therapy at our institution from May 2006 to September 2010, retrospectively. Amrubicin was administered intravenously at 40 or 45 mg/m2 on day 1 to 3 of 3-4 weeks until disease progression or development of intolerance. Results: Profile of patients included: median age was 57 years (range 25–74); Male/Female=5/6; PS 0/1= 7/4; and Masaoka stage IVA/IVB/recurrence=7/2/2. All patients had received no prior chemotherapy. The median number of treatment cycles was 4 (range 3-6). A partial response was achieved in 1 patient and 10 patients exhibited stable disease. The overall response rate was 9%, but 3 patients had at least a 20% reduction in tumor size with amrubicin. The median reduction rate in tumor size was 13% (range 0-40). The median progression-free survival period was 5.4 months (range 2.3-15.8 months). The median overall survival has not been reached although a median follow-up time was 2.5 years. Based on the Kaplan-Meier method, the estimated 3-year survival rate was 83%. The most common adverse events were hematological toxicities. Five patients had grade 3/4 neutropenia, but febrile neutropenia was not observed. Non-hematological grade 3 toxicities were less frequent. There were no treatment-related deaths. Conclusions: Single-agent amrubicin showed modest activity and acceptable safety profile as chemotherapy for advanced or recurrent thymoma. Additional testing of amrubicin combined with cisplatin in this disease is warranted.

Phase II study of amrubicin (AMR) for patients (pts) with non-small cell lung cancer (NSCLC) as third-line or fourth-line chemotherapy: Hokkaido Lung Cancer Clinical Study Group trial (HOT) 0901.

7571 Background: Although an increasing number of NSCLC pts receive third-line chemotherapy with the established benefit of second-line chemotherapy, the role of cytotoxic agent in this setting has not yet been well defined prospectively. AMR, third-generation synthetic anthracycline agent, has found favorable clinical activity and acceptable toxicity for NSCLC as well as small cell lung cancer. This prospective trial was conducted to evaluate the efficacy and safety of AMR for NSCLC pts as third-line or fourth-line chemotherapy. Methods: Eligible pts had a performance status 0 to 2, failure of second-line or third-line chemotherapy, and adequate organ function. Pts received AMR 35 mg/m2 intravenously on days 1-3 every 3 weeks. The primary endpoint was disease control rate (DCR: CR + PR + SD). Secondary endpoints were overall survival (OS), progression-free survival (PFS), response rate (CR + PR), and toxicity profile. The estimated accrual was 37 pts to confirm a DCR of 50% as desirable target level and a DCR of 30 % as uninteresting with alpha = 0.05 and beta = 0.20. Results: From August 2009 to May 2011, 41 pts were enrolled from 10 institutions. Patient characteristics were: male/female 29/12; median age 66 (range 43–74); performance status 0/1/2 16/24/1; adenocarcinoma/squamous cell carcinoma/large cell carcinoma/not other specified 30/8/2/1; EGFR mutation positive/negative/unknown 7/26/8; treatment lines 3rd/4th 26/15. The median number of treatment cycles was 2 (range 1-9). The objective responses were CR 0, PR 4, SD 22, PD 14, and NE 1, giving a DCR of 61.0% (95% CI, 46.0-75.9%). Overall response rate was 9.8% (95% CI, 0.6-18.8%). Median PFS was 2.6 months, whereas median survival time was not reached. Grade 3/4 hematological toxicities were neutropenia (68%), anemia (12%), thrombocytopenia (12%), and febrile neutropenia (17%). Grade 3/4 non-hematological toxicities were anorexia (12%), nausea (10%), and pneumonitis (2%). No treatment-related death was observed. Conclusions: AMR shows significant clinical activity with acceptable toxicities as third-line or fourth-line chemotherapyfor advanced NSCLC.

Phase I study to assess pharmacokinetics (PK), QT/QTc effect, and safety of amrubicin in patients (pts) with advanced solid tumors.

7073 Background: Amrubicin (AMR), a 3rd-generation synthetic anthracycline has shown promising activity in solid tumors, including small cell lung cancer (SCLC) without cardiotoxicity. This intensi...

Late phase II study of amrubicin in previously untreated patients with non-Hodgkin's lymphoma (NHL).

8097 Background: We evaluated the efficacy and safety of amrubicin, a third generation synthetic anthracycline, in combination with cyclophosphamide, vincristine and prednisolone (ACOP) in patients with previously untreated aggressive non-Hodgkin's lymphoma (NHL). Methods: Previously untreated patients with intermediate or high grade NHL were treated with 8 cycles of amrubicin, 100 mg/m2, cyclophosphamide, 750 mg/m2, and vincristine, 1.4 mg/m2 (maximum 2.0 mg), on day 1, and prednisolone, 60 mg/m2/day day 1-5 every 21 days. Patients were evaluated for response and left ventricular ejection fraction (LVEF) every 2 cycles, and electrocardiogram at every cycle. The primary endpoint was response rate; secondary endpoints were survival, cardiac safety, and general safety. Results: Fifty-six patients were eligible and received a median of 8 treatment cycles. The median follow- up period was 57.1 months. Most patients had diffuse large B-cell lymphoma (76.8%). The response rate was 92.9%; the complete response (CR) and CRu rate was 69.6%. The 2- and 5-years survival rates were 76.2% and 58.7%, respectively. Reversible myelosuppression was the most common adverse event. Grade 3/4 neutropenia, anemia, thrombocytopenia and febrile neutropenia were reported in 82.5%, 19.3%, 8.8% and 7% of patients, respectively. There were no treatment-related deaths or patients experiencing cardiomyopathy. LVEF did not change during the course of treatment. Conclusions: The response rate and survival in non-Hodgkin's lymphoma patients treated with ACOP were comparable to those achieved with CHOP in other studies, but ACOP had virtually no reduction of LVEF up to a cumulative amrubicin dose of 800 mg/m2. This suggests that amrubicin has little chronic cardiotoxicity. ACOP should be evaluated in combination with rituximab (R) and then compared to R-CHOP. No significant financial relationships to disclose.

A phase II study of amrubicin combined with carboplatin for elderly patients with small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0405

BackgroundAmrubicin, a new anthracycline agent, has shown high activity for small-cell lung cancer (SCLC) in previous studies. However, a combination regimen with amrubicin and platinum has been investigated little. On the basis of previous phase I study, we conducted this study to evaluate the efficacy and the safety of amrubicin and carboplatin for elderly patients with SCLC. MethodsChemotherapy-naive elderly patients with SCLC received amrubicin (35 mg/m2, days 1–3) and carboplatin [area under the curve (AUC) 4.0, day1] every 3 weeks. The primary end point was overall response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival and toxicity profile. ResultsFrom January 2005 to November 2007, 36 patients were enrolled [median age 76 (range 70–83); ECOG performance status of zero and one in 17 and 19 patients, respectively]. One complete response and 31 partial responses were observed (ORR 89%). Median PFS was 5.8 months and median survival time was 18.6 months. Grade 3–4 neutropenia was observed in 97% of the patients and six patients (17%) suffered from grade 3–4 febrile neutropenia. Other toxic effects were moderate and treatment-related death was not observed. ConclusionsAmrubicin combined with carboplatin is quite effective for SCLC with acceptable toxic effects even for the elderly population. Further evaluation of this regimen is warranted.

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

Purpose This study was designed to confirm the efficacy and safety of amrubicin, a new anthracycline agent, in patients with previously treated non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Methods Eligible patients were required to have recurrent or refractory NSCLC and SCLC after one or two previous chemotherapy regimens. All patients received intravenous amrubicin 35 mg/m 2 on days 1–3 every 3 weeks. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results Sixty-six patients (37 NSCLC and 29 SCLC) were assessable for efficacy and safety evaluation. Grade 3 or 4 neutropenia was observed in 39.4% of all patients (NSCLC, 37.8%; SCLC, 41.4%). Nonhematological toxicities were mild. No treatment-related death was observed. The ORRs were 13.5% (95% CI, 4.5–28.8%) in NSCLC and 44.8% (95% CI, 26.4–64.3%) in SCLC. In SCLC, ORRs were 60.0% in the sensitive relapse and 36.8% in the refractory relapse ( p = 0.2332). In NSCLC, the PFS, OS, and 1-year survival were 3.3 months, 12.0 months, and 35.3%, respectively. In SCLC, the PFS, OS, and 1-year survival were 4.0 months, 12.0 months, and 46.7%, respectively. Conclusions Amrubicin is an active and well-tolerated regimen in patients with previously treated lung cancer. Amrubicin 35 mg/m 2 seems to achieve similar efficacy with less toxicity than amrubicin 40 mg/m 2 in this patient population. These results warrant further evaluation in previously treated lung cancer.

Phase II study of amrubicin (AMR) in patients (pts) with non-small cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy: WJTOG0401

8059 Background: AMR is a totally synthetic 9-aminoanthracycline and a novel topoisomerase II inhibitor. AMR has shown promising clinical activity for advanced NSCLC as well as SCLC. This trial was conducted to evaluate the efficacy and safety of AMR for pts with NSCLC previously treated with platinum-based chemotherapy. Methods: Eligible pts had a performance status 0 to 1, previous treatment with one platinum-based chemotherapy for advanced NSCLC, and adequate organ function. Pts received AMR 40 mg/m2 intravenously on days 1–3 every 3 weeks. The primary endpoint was the objective response rate, which determined the sample size based on an optimal two-stage design. With the target activity level of 18% and the lowest response rate of interest set at 5%, 60 eligible patients were required with a 90% power to accept the hypothesis and a 5% significance level to reject the hypothesis. Results: Sixty-one pts (median age, 63 years; range 51–74 years) were enrolled. The median treatment cycles were 2 (range, 1–15). No complete responses and 7 partial responses were observed, giving an overall response rate of 11.5% (95% CI, 4.7–22.2%). Twenty patients (32.8%) had stable disease and 34 patients (55.7%) had progressive disease as the best response. The overall disease control rate (complete response + partial response + stable disease) was thus 44.3% (95% CI, 31.5–57.6%). The median overall survival and 1-year survival rate were 8.5 months and 32.0%, respectively. Grade 3/4 hematological toxicities were neutropenia (82%), anemia (27.9%) and thrombocytopenia (24.6%). Grade 3/4 non-hematological toxicities were anorexia (9.8%), febrile neutropenia (29.5%) and pneumonitis (1.6%). No treatment-related death and cardiac toxicity were observed. Conclusions: AMR exhibits significant activity with manageable toxicities as second-line therapy for advanced NSCLC. [Table: see text]

Retrospective analysis of efficacy and safety of amrubicin in refractory and relapsed small-cell lung cancer

Amrubicin, a totally synthetic 9-aminoanthracycline, was evaluated retrospectively for the treatment of refractory and relapsed small-cell lung cancer (SCLC). Retrospective analysis was performed in 32 patients. Amrubicin was infused over 5 min on days 1-3, with courses repeated at 3- or 4-week intervals. Amrubicin was given at a dose of 45 mg/m(2) per day, 40 mg/m(2) per day, 35 mg/m(2) per day, 30 mg/m(2) per day, or 25 mg/m(2) per day depending on medical conditions (patients' age and performance status [PS]), and the dose was modulated according to myelosuppression. The median number of treatment cycles was 3 (range, 1-6). Seventeen patients (53.1%) had a partial response. Median progression-free survival time for all patients was 96 days, and median survival time was 166 days. Grade 3 or 4 hematologic toxicities comprised neutropenia (78.1%), anemia (65.6%), and thrombocytopenia (50.0%). Febrile neutropenia was observed in 8 patients (25.0%). Nonhematologic toxicities were mild. Treatment-related death was observed in 1 patient. Treatment with amrubicin appeared effective in SCLC patients previously treated with chemotherapy, although it was not necessarily safe, because of myelosuppression. Further research is warranted to investigate amrubicin treatment for patients with SCLC.

Phase II study of amrubicin in previously untreated patients with extensive-disease small cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) study

To evaluate the efficacy and safety of amrubicin, (+)-(7S, 9S)-9-acetyl-9-amino-7-[(2-deoxy-beta-D-erythro-pentopyranosyl )oxy]-7,8,9,10-tetrahydro-6,11-dihydroxy-5,12-naphthacenedione hydrochloride, in previously untreated patients with extensive-disease small cell lung cancer (SCLC). A total of 35 previously untreated patients with extensive-disease SCLC were entered into the study. Amrubicin was given by daily intravenous infusion at 45 mg/m(2)/day for 3 consecutive days, every 3 weeks. Unless there was tumor regression of 25% or greater after the first cycle, or 50% or greater after the second cycle, treatment was switched to salvage chemotherapy in combination with etoposide (100 mg/m(2), days 1, 2, and 3) and cisplatin (80 mg/m(2), day 1). Of the 35 patients entered, 33 were eligible and assessable for efficacy and toxicity. Of the 33 patients, 3 (9.1%) had a complete response (95% confidence interval [CI], 1.9-24.3%) and 22 had a partial response, for an overall response rate of 75.8% (95% CI, 57.7-88.9%). Median survival time was 11.7 months (95% CI, 9.9-15.3 months), and 1-year and 2-year survival rates were 48.5% and 20.2%, respectively. The most common toxicity was hematologic. Non-hematologic toxicity of grade 3 or 4 was only seen in 3 patients with anorexia (9.1%) and 1 patient with alopecia (3.0%). Salvage chemotherapy was administered to only 6 patients. Amrubicin was active for extensive-disease SCLC with acceptable toxicity. Further studies in combination with other agents for SCLC are warranted.