A phase II trial of single-agent amrubicin (AMR) in patients with extensive disease small cell lung cancer (ED-SCLC) that is refractory or progressive within 90 days of completion of first-line platinum-based chemotherapy

Ettinger, David S.; Jotte, Robert M.; Gupta, V. D.; Allen, Amanda; Oliver, J

doi:10.1200/jco.2008.26.15_suppl.8041

Cited by 13 publications

(13 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ettinger paid attention to the interracial differences in NQ01, a doxorubicin efflux transporter, and wondered whether the significant antitumour activity of amrubicin in Japanese patients would also be noted in US and European patients [22] . With respect to this issue, two reports were presented at the poster discussion of the annual meeting of the American Society of Clinical Oncology (ASCO) 2008 [23,24] : the reports revealed that the antitumour efficacy was inferior, although only slightly, to those obtained in Japanese patients, whereas both the frequency and seriousness of marrow depression, the major adverse effect, were lower in the US and European patients than in the Japanese. Further investigation is warranted for the purpose of determining whether these findings might have been related to the interracial differences as has been suggested, or due to the setting of optimal dosage levels in the US and European studies.…”

Section: Kuratamentioning

confidence: 97%

Amrubicin for the treatment of advanced lung cancer

Kurata

2009

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

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. OverviewLung cancer is the leading cause of cancer-related death in many countries. The disease can be classified into two types, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC accounting for 80 -85% of all cases.Approximately 50% of the patients with NSCLC have advanced disease. The standard therapy for patients with good performance status (PS) is systemic chemotherapy. Based on the results of a meta-analysis, cisplatin (CDDP)-based doublets are considered the best available therapy for patients with metastatic NSCLC, with a 10% improvement in the 1-year survival rate compared to the best supportive care [1] . As several new agents with significant activity against NSCLC have been introduced, such as paclitaxel, docetaxel, vinorelbine and gemcitabine, any of these agents used in combination with a platinum agent has improved outcomes compared to older agents [2] and each regimen provides a similar survival outcome [3,4] . However, unfortunately, almost all patients recur. Relapsed patients who still have a good PS receive second-line chemotherapy, which is considered a standard of care. Docetaxel, pemetrexed and EGFR inhibitor, erlotinib, are used in this setting. Recently, some molecular targeted agents have been developed in the treatment of NSCLC. A large, randomised Phase III study showed clear survival benefit by adding bevacizumab, an angiogenesis inhibitor, to the combination chemotherapy of carboplatin (CBDCA) and paclitaxel [5] . In addition, EGFR inhibitors, such as erlotinib and gefitinib, were very effective in a special molecularly defined population of patients harbouring EGFR somatic mutations [6,7] . For these reasons, much interest is concentrated on the development of molecular targeted agents. However, as the strategy of combination therapy with molecular targeted agents and cytotoxic agents is becoming more important, the development of cytotoxic agents is also similarly growing in importance.

show abstract

Section: Kuratamentioning

confidence: 97%

Amrubicin for the treatment of advanced lung cancer

Kurata

2009

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

show abstract

“…Several other cytotoxic agents, including taxanes, gemcitabine, vinorelbine, irinotecan and pemetrexed, have been investigated as second-line treatment, in either single-agent or combination treatment (table 3) [41,65,[76][77][78][79][80][81][82][83][84][85][86][87][88][89][90]. Some agents, such as paclitaxel and irinotecan, have shown some degree of activity in phase II trials.…”

Section: Second-line Treatment For Es-sclcmentioning

confidence: 99%

“…Interestingly, the response rate and median survival were similar in both sensitive and resistant patients. A phase II trial in the USA has investigated single-agent amrubicin in patients with refractory or resistant SCLC [89]. Activity was observed, and the most frequently observed toxicity was myelosuppression, but no anthracycline-induced cardiotoxicity was noted.…”

Section: Second-line Treatment For Es-sclcmentioning

confidence: 99%

Treatment of extensive-stage small cell lung carcinoma: current status and future prospects

Demedts

Vermaelen²,

Meerbeeck³

2009

European Respiratory Journal

183

162

View full text Add to dashboard Cite

Small cell lung cancer (SCLC) is an aggressive lung tumour strongly associated with cigarette smoking, with patients often presenting with metastatic disease at the time of diagnosis. Although SCLC is very chemoradiosensitive and high response rates are obtained with treatment, relapse rates are high and the prognosis remains very poor.In limited-stage SCLC, the overall survival rate has been significantly improved by adding dosehyperfractionated thoracic radiotherapy and prophylactic cranial irradiation to systemic chemotherapy. In contrast, little progress has been made in the treatment of extensive-stage SCLC (ES-SCLC), apart from the recently documented survival gain by the addition of prophylactic cranial irradiation.First-line therapy in ES-SCLC currently consists of chemotherapy, combining a platinum drug with either etoposide or irinotecan as a possible alternative.New treatments are needed in order to improve the prognosis of ES-SCLC, as median survival with current standard treatment is still only 9-10 months from diagnosis. The present review focuses on the management of ES-SCLC, with special attention to the development of new treatment options.KEYWORDS: Chemotherapy, extensive disease, radiotherapy, small cell lung cancer, treatment S mall cell lung cancer (SCLC) is an aggressive malignant disease, with the majority of patients presenting with distant metastasis at diagnosis. A separate staging system has been developed for SCLC, classifying SCLC as limited or extensive disease [1]. The International Association for the Study of Lung Cancer defines limited-stage SCLC (LS-SCLC) as: ''disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal, and ipsilateral and contralateral supraclavicular nodes and should also include patients with ipsilateral pleural effusion independent of whether cytology is positive or negative '' [2]. Patients with SCLC who do not fit this definition are considered to have extensive-stage SCLC (ES-SCLC). This staging system was used to select the appropriate treatment regimen: chemotherapy in combination with thoracic radiotherapy in patients with LS-SCLC, and chemotherapy alone in patients with ES-SCLC. Recent data suggest that the tumour, node, metastasis classification traditionally reserved for the staging of nonsmall cell lung cancer (NSCLC) can also be applied for the staging of SCLC [3].

show abstract

“…Ettinger et al displayed an update of a phase II trial to investigate effi cacy and safety of single-agent amrubicinfi rst presented at last year's ASCO -enroling 75 Western patients with ED-SCLC refractory to prior 1st line platinumbased chemotherapy [12]. Th e primary endpoint of the study (point estimate: ORR 18%) was met with an ORR of 21% (95% CI = 13.6-31.9%).…”

Section: Amrubicin (Amr) Phase II Results In Ed-sclc 2nd Linementioning

confidence: 98%

SCLC – Asco 2009

Ploner

2009

memo

View full text Add to dashboard Cite

For years interest in developing new treatment strategies in SCLC has lagged behind the eff orts addressing NSCLC. Th is trend could easily be followed during the ASCO 2009 meeting. Fifty-two abstracts relating to SCLC were exhibited, whereas 392 abstracts covered NSCLC research topics. None of the presentations dealing with SCLC showed successful phase III results no results were presented in the lung cancer oral presentation session. We are left with eff orts in challenging the fi rst-line standard regimen of etoposide/platinum (EP) with the irinotecan/platinum (IP) regimen as an alternative treatment choice with comparable results but diff erent toxicity. Randomised phase II results with amrubicin seem to support the use of second-line treatment in an otherwise chemo-resistant and desperate disease. In various trials most of the investigated new targeting agents did not lead to a reproducible improvement in the outcome of SCLC patients. After ASCO 2009 it seems that progress in the treatment of SCLC requires not only a tailored medical approach, which is diffi cult to achieve, but also changes in therapeutical strategies in radiotherapy and surgery for LD-SCLC.

show abstract

A phase II trial of single-agent amrubicin (AMR) in patients with extensive disease small cell lung cancer (ED-SCLC) that is refractory or progressive within 90 days of completion of first-line platinum-based chemotherapy

Cited by 13 publications

References 0 publications

Amrubicin for the treatment of advanced lung cancer

Amrubicin for the treatment of advanced lung cancer

Treatment of extensive-stage small cell lung carcinoma: current status and future prospects

SCLC – Asco 2009

Contact Info

Product

Resources

About