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Japanese Journal of Clinical Oncology Oct 2013Thymic carcinoma is a rare mediastinal neoplasm, and the prognosis of patients with advanced thymic carcinoma is poor. No standard chemotherapeutic regimen has yet been...
OBJECTIVE
Thymic carcinoma is a rare mediastinal neoplasm, and the prognosis of patients with advanced thymic carcinoma is poor. No standard chemotherapeutic regimen has yet been established for the disease. This is the first report to evaluate the role of amrubicin, a novel anthracycline anticancer drug, in second-line and beyond treatment for patients with platinum-refractory advanced thymic carcinoma.
METHODS
This study was a review of thymic carcinoma patients who had received amrubicin monotherapy between June 2003 and December 2011 for the progression of disease previously treated with platinum-based chemotherapy. Amrubicin was administered at 35 or 40 mg/m(2) for three consecutive days every 3 weeks, until progression.
RESULTS
Nine patients with recurrent thymic carcinoma were registered. Their median age was 61 years (range 45-72), and the patients included five males and four females. All nine patients had Masaoka's Stage IVb disease. There were three squamous cell carcinomas, one adenocarcinoma, one small-cell carcinoma and two other histological types. The mean number of chemotherapy cycles was five (range 2-13). Grade 3 or higher toxicities included mainly neutropenia (55.5%), anemia (25.0%) and febrile neutropenia (11.1%). No treatment-related deaths were observed. The response rate was 44.4% (95% confidence interval: 19-73). The median progression-free survival after the amrubicin monotherapy was 4.9 months, while the median overall survival was 6.4 months.
CONCLUSIONS
Single-agent amrubicin was found to be potentially useful as second-line and beyond chemotherapy for patients with advanced thymic carcinoma. Further multi-institutional prospective studies are warranted.
Topics: Adenocarcinoma; Aged; Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Disease-Free Survival; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Platinum Compounds; Retrospective Studies; Thymoma; Thymus Neoplasms; Treatment Outcome
PubMed: 23917962
DOI: 10.1093/jjco/hyt106 -
Lung Cancer (Amsterdam, Netherlands) Mar 2018First-line treatment for patients with extensive-stage small cell lung cancer (SCLC) includes treatment with platinum-based combination chemotherapy. Amrubicin is a...
PURPOSE
First-line treatment for patients with extensive-stage small cell lung cancer (SCLC) includes treatment with platinum-based combination chemotherapy. Amrubicin is a synthetic anthracycline with single-agent activity in relapsed/refractory SCLC. In an attempt to improve treatment efficacy, we evaluated amrubicin/carboplatin as first-line therapy for extensive-stage SCLC.
PATIENTS AND METHODS
In this multicenter phase II trial, patients received amrubicin (30 mg/m daily on Days 1, 2, and 3) and carboplatin (AUC = 5 on Day 1); cycles were repeated every 21 days for 4 cycles. Pegfilgrastim (6 mg subcutaneously) was administered on Day 4 of all cycles. Overall survival (OS) proportion at 1 year was the primary endpoint. The target 1-year OS rate was 47%, an improvement of 35% from historical results with carboplatin/etoposide.
RESULTS
Eighty patients received study treatment, and 62% completed the planned 4 courses. The overall response rate was 74% (13% complete responses). The 1-year survival rate was 38% (95% CI: 25, 50). The median survival was 10 months. Myelosuppression was severe but manageable.
CONCLUSIONS
The combination of amrubicin/carboplatin was an active first-line treatment for extensive stage SCLC, but showed no indication of increased efficacy compared to standard treatments. Severe myelosuppression was common with this regimen, in spite of prophylactic pegfilgrastim. These results are consistent with those of other trials in showing no role for amrubicin in the first-line treatment of SCLC.
Topics: Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Female; Filgrastim; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Polyethylene Glycols; Small Cell Lung Carcinoma; Survival Analysis; Treatment Outcome
PubMed: 29496254
DOI: 10.1016/j.lungcan.2018.01.007 -
Cancers Aug 2022Adding an immune checkpoint inhibitor to chemotherapy to treat extensive-stage small cell lung cancer is effective. However, there are no reports of an effective...
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.
PubMed: 36010946
DOI: 10.3390/cancers14163953 -
Anticancer Research Apr 2012Amrubicin is an active agent for the treatment of small-cell lung cancer (SCLC). However, there have been no reports of long-term amrubicin use.
BACKGROUND
Amrubicin is an active agent for the treatment of small-cell lung cancer (SCLC). However, there have been no reports of long-term amrubicin use.
PATIENTS AND METHODS
Twelve patients with SCLC who were treated with eight or more cycles of amrubicin chemotherapy were retrospectively reviewed.
RESULTS
The median number of cycles of amrubicin chemotherapy received by the patients was 12 (range=8-20), and the median cumulative dose of amrubicin was 2076 mg (range=1200-2856 mg). The median survival time of the study patients was 1104 days (range=459-1997 days). The main adverse events observed during amrubicin chemotherapy were leukopenia and neutropenia. The cardiothoracic ratio (CTR), expressed as the mean (standard deviation) of the values measured at the initiation and termination of amrubicin chemotherapy was 46.2 (4.0), and 46.1 (5.1), respectively. The change in CTR did not reach statistical significance (p=0.92).
CONCLUSION
Long-term amrubicin chemotherapy is a safe and effective treatment that is associated with a good survival prognosis in properly selected patients.
Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Carcinoma, Small Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged
PubMed: 22493380
DOI: No ID Found -
Cancer Chemotherapy and Pharmacology Apr 2015Extrapulmonary neuroendocrine carcinomas (EPNEC) are rarely observed and are associated with poor outcomes. Based on the clinicopathological similarity, treatment used...
PURPOSE
Extrapulmonary neuroendocrine carcinomas (EPNEC) are rarely observed and are associated with poor outcomes. Based on the clinicopathological similarity, treatment used for small cell lung carcinoma has also been employed for EPNEC, but the response to such therapy has not been well examined. The goal of this study was to investigate amrubicin (AMR) monotherapy as a salvage therapy for EPNEC arising from digestive organs.
METHODS
Patients with EPNEC of the digestive organs who had prior platinum-based chemotherapy and were subsequently treated with AMR between July 2005 and December 2013 at any one of four institutions were retrospectively examined to characterize the safety and efficacy of AMR.
RESULTS
Thirteen patients (ten males, three females; median age 64 years) were examined. Primary cancer sites included stomach (n = 6), rectum (n = 3), esophagus (n = 2), liver (n = 1) and pancreas (n = 1). Prior irinotecan- and etoposide-containing chemotherapies were used in ten and six patients, respectively. Median initial dose of AMR was 40 mg/m(2)/day for three consecutive days, and median of treatment cycles was 4 (range 1-9). The objective response rate (ORR) was 38.5%. Median progression-free survival (PFS) and overall survival (OS) were 107 (range 22-275) and 215 days (range 71-535), respectively. Common severe adverse events (grade 3/4) were neutropenia (84.6%) and febrile neutropenia (30.8%). Patient with longer platinum-free interval (>90 days) exhibited longer PFS and OS than those with shorter platinum-free interval (190 vs. 63 days and 348 vs. 145 days, respectively).
CONCLUSIONS
AMR showed evidence of clinical activity and safety when used for the treatment of EPNEC. It might be especially useful for populations with sensitive relapse.
Topics: Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Neuroendocrine; Cisplatin; Digestive System Neoplasms; Disease-Free Survival; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Retrospective Studies; Salvage Therapy
PubMed: 25702050
DOI: 10.1007/s00280-015-2706-y -
Japanese Journal of Clinical Oncology Jul 2011No standard chemotherapy has been established yet for large-cell neuroendocrine carcinoma of the lung. Amrubicin is active for both small cell and non-small cell lung...
OBJECTIVE
No standard chemotherapy has been established yet for large-cell neuroendocrine carcinoma of the lung. Amrubicin is active for both small cell and non-small cell lung cancers, but its activity for large-cell neuroendocrine carcinoma is still unknown.
METHODS
From January 2002 to December 2009, 18 patients with previously treated advanced large-cell neuroendocrine carcinoma received amrubicin monotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively.
RESULTS
The patients comprised 17 males and one female with a median age of 62 years (range, 51-77). Fourteen and four patients had a performance status of 0-1 and 2, respectively. Thirteen (72%) patients had received one prior chemotherapy, while the others had received two or more chemotherapies. All the patients had received platinum-based chemotherapy before the amrubicin treatment. A total of 63 cycles of amrubicin chemotherapy was administered in the 18 patients, with a median number of cycles per patient of 2.5 (range, 1-10). The median dose of amrubicin in the 63 cycles was 40 (range, 30-45) mg/m(2)/day for 3 days. Grades 3-4 neutropenia, thrombocytopenia and anemia were seen in 89, 17 and 22% of the patients, respectively. Grade 3 febrile neutropenia occurred in 33% of the patients. Non-hematological toxicity was generally mild and manageable. There were five cases of partial response, six of stable disease and six of progressive disease among the 18 patients, yielding an objective response rate of 27.7%. The median progression-free and overall survivals of the patients were 3.1 and 5.1 months, respectively.
CONCLUSION
Amrubicin was potentially active against previously treated large-cell neuroendocrine carcinoma.
Topics: Aged; Anthracyclines; Antineoplastic Agents; Carcinoma, Large Cell; Carcinoma, Neuroendocrine; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Lung Neoplasms; Male; Middle Aged; Retrospective Studies; Treatment Outcome
PubMed: 21636606
DOI: 10.1093/jjco/hyr065 -
International Journal of Clinical... Jul 2023Amrubicin (AMR) is one of the most active agents for small-cell lung cancer (SCLC). However, hematologic toxicity and infection at a commonly used dose (40 mg/m) is...
BACKGROUND
Amrubicin (AMR) is one of the most active agents for small-cell lung cancer (SCLC). However, hematologic toxicity and infection at a commonly used dose (40 mg/m) is problematic; the optimal dose remains undetermined.
PATIENTS AND METHODS
To evaluate the optimal dose of AMR in terms of efficacy and safety, we reviewed consecutive data on patients with relapsed SCLC who received AMR at doses of 40, 35, and 30 mg/m (on days 1-3) at Nippon Medical School Hospital between October 2010 and November 2021.
RESULTS
We reviewed the data of 86 patients (20, 45, 27 who received AMR doses of 40, 35, 30 mg/m, respectively) according to our study criteria. For patients ≥ 75 years, the proportion who received second-line treatment tended to be higher in the 30-35 mg/m group. Objective response rates were 37/46/35%, median progression-free survival (PFS) were 3.0/4.7/3.2 months, and median overall survival (OS) were 7.8/16.3/8.0 months, respectively. Grade 4 neutropenia occurred in 58/39/31% of patients, which was higher for the 40 mg/m group. The incidence of febrile neutropenia did not differ between groups. Multivariate analysis identified the AMR dose was not associated with longer PFS and OS.
CONCLUSION
Treatment with AMR between 30 and 35 mg/m showed relatively mild hematologic toxicity compared with AMR at 40 mg/m, without any significant difference in efficacy. Lower dose of AMR for relapsed SCLC could be a promising treatment option.
Topics: Humans; Anthracyclines; Antineoplastic Agents; Lung Neoplasms; Retrospective Studies; Small Cell Lung Carcinoma; Treatment Outcome
PubMed: 37171692
DOI: 10.1007/s10147-023-02343-9 -
Internal Medicine (Tokyo, Japan) 2010The novel anthracycline agent amrubicin, has been approved in Japan to treat small and non-small cell lung cancers (SCLC and NSCLC). The present study evaluates the...
OBJECTIVE
The novel anthracycline agent amrubicin, has been approved in Japan to treat small and non-small 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 METHODS
This retrospective study analyzed data from 51 patients (<70 years of age, n=29; > oor =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 > or =70 years. The rate of hematological toxicities (> or = Grade 3) also did not significantly differ between the two age groups (leukopenia, 48.3% and 59.1% for age <70 and > or =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.
Topics: Age Factors; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Lung Neoplasms; Male; Middle Aged; Recurrence; Retrospective Studies; Salvage Therapy; Topoisomerase II Inhibitors; Treatment Outcome
PubMed: 20823645
DOI: 10.2169/internalmedicine.49.3606 -
Breast Cancer Research and Treatment Dec 2014Amrubicin is a synthetic anthracycline which has been shown in preclinical studies to have broad-spectrum anti-tumor activity and a lower potential for cardiotoxicity as...
Amrubicin is a synthetic anthracycline which has been shown in preclinical studies to have broad-spectrum anti-tumor activity and a lower potential for cardiotoxicity as compared to doxorubicin. We conducted a phase 1/2 trial of single-agent amrubicin as second- or third-line treatment for women with metastatic breast cancer. Women with metastatic HER2-negative breast cancer who had normal cardiac function and measurable disease, received intravenous (IV) amrubicin every 3 weeks. Prophylactic treatment with granulocyte colony-stimulating factors (G-CSFs) was recommended. Escalating amrubicin doses were administered in a 3 + 3 design in the phase 1 portion to determine the maximum tolerated dose. Achievement of a median PFS ≥4.5 months would warrant further development of amrubicin in this setting. Seventy-eight women (median age 58 years) were treated (phase 1, 15 patients; phase 2, 63 patients). An amrubicin dose of 110 mg/m(2) every 3 weeks was selected as the phase 2 dose, and 66 patients were treated. Twelve of 66 patients (18%) achieved objective response, and the clinical benefit rate was 42%. Median PFS was 4 months (95% CI 2.5, 5.8). Neutropenia was the most common grade 3/4 toxicity, observed in 29 patients (44%). One patient experienced an asymptomatic transient left ventricular ejection fraction decline (grade 3). Although the study did not meet the predefined PFS, amrubicin was well tolerated at 110 mg/m(2) IV when administered every 3 weeks with prophylactic G-CSF, and was an active second- or third-line treatment for metastatic HER2-negative breast cancer.
Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease-Free Survival; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Maximum Tolerated Dose; Middle Aged; Receptor, ErbB-2; Treatment Outcome
PubMed: 25374098
DOI: 10.1007/s10549-014-3189-y -
Molecular and Clinical Oncology May 2017There is no standard chemotherapy for pulmonary large-cell neuroendocrine carcinoma (LCNEC) and this type of cancer is difficult to diagnose using biopsy specimens. At...
Amrubicin monotherapy may be an effective second-line treatment for patients with large-cell neuroendocrine carcinoma or high-grade non-small-cell neuroendocrine carcinoma.
There is no standard chemotherapy for pulmonary large-cell neuroendocrine carcinoma (LCNEC) and this type of cancer is difficult to diagnose using biopsy specimens. At the Shizuoka Cancer Center, when small biopsy specimens are used, they are diagnosed as high-grade non-small-cell neuroendocrine carcinoma (HNSCNEC) and the patients are treated according to the small-cell lung cancer (SCLC) guidelines. Amrubicin is an effective second-line treatment for patients with SCLC, although it remains unclear whether amrubicin monotherapy is effective for patients with LCNEC or HNSCNEC. Between September, 2004 and December, 2013, 18 patients with advanced LCNEC or HNSCNEC received amrubicin monotherapy in the second-line setting. The efficacy and toxicity of this treatment were retrospectively assessed. A total of 6 patients had LCNEC and 12 patients had HNSCNEC. The patients included 13 men, and the median age was 66 years (range, 57-82 years). A total of 16 patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. All the patients had received platinum-based chemotherapy as first-line treatment, and the median number of amrubicin cycles per patient was 4 (range, 1-9). The overall response rate was 11.1%. The median progression-free and overall survival were 4.0 and 9.1 months, respectively. Grade 3 or 4 neutropenia was observed in 44% of the patients, and grade 3 febrile neutropenia occurred in 17% of the patients. One patient developed pneumonia and succumbed to the disease. Non-hematological toxicities were generally mild and manageable. Therefore, the efficacy of amrubicin in the second-line setting for patients with LCNEC or HNSCNEC is limited. Development of new drugs and/or treatment strategies is warranted.
PubMed: 28529747
DOI: 10.3892/mco.2017.1198