Phase II Study of Amrubicin As Second-Line Therapy in Patients With Platinum-Refractory Small-Cell Lung Cancer

Ettinger, David S.; Jotte, Robert M.; Lorigan, Paul; Gupta, Vicram; Garbo, Lawrence; Alemany, Carlos; Conkling, Paul; Spigel, David R.; Dudek, Arkadiusz Z.; Shah, Chirag; Salgia, Ravi; McNally, Richard; Renschler, Markus F.; Oliver, Jennifer

doi:10.1200/jco.2009.26.7682

Cited by 115 publications

(85 citation statements)

References 23 publications

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“…The present study showed a RR of 20.0% and a median PFS of 2.6 months. These outcomes were comparable with those reported for amrubicin chemotherapy for SCLC in the second-line setting; the reported ranges of RR and median PFS in phase II studies were 17-52% and 2.6-4.0 months, respectively [9][10][11]13]. Considering these facts, amrubicin therapy appears to be potentially active for platinum-refractory gastroenteropancreatic NEC.…”

Section: Discussionsupporting

confidence: 71%

“…Amrubicin, a totally synthetic 9-aminoanthracycline that acts as a potent topoisomerase II inhibitor, has been developed for the treatment of SCLC. In the secondline setting, amrubicin monotherapy showed a RR of 17%-52% in patients with SCLC [9][10][11]. In five patients with gastrointestinal NEC, amrubicin monotherapy was shown to be potentially effective [12].…”

Section: Introductionmentioning

confidence: 99%

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Amrubicin monotherapy for patients with platinum-refractory gastroenteropancreatic neuroendocrine carcinoma.

Ando

Hosokawa

Yoshita

et al. 2015

JCO

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Objective. Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as first-line treatment; however, the role of salvage chemotherapy remains unknown. This study aimed to analyze the efficacy and safety of amrubicin monotherapy in patients with platinum-refractory gastroenteropancreatic NEC. Methods. Among 22 patients with advanced gastroenteropancreatic NEC, 10 received amrubicin monotherapy between September 2007 and May 2014 after failure of platinum-based chemotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively. Results. Eight males and two females (median age, 67 years (range, 52-78)) received platinum-based chemotherapy, including cisplatin plus irinotecan ( = 7, 70%), cisplatin plus etoposide ( = 2, 20%), and carboplatin plus etoposide ( = 1, 10%) before amrubicin therapy. Median progression-free survival and overall survival after amrubicin therapy were 2.6 and 5.0 months, respectively. Two patients had partial response (20% response rate), and their PFS were 6.2 months and 6.3 months, respectively. Furthermore, NEC with response for amrubicin had characteristics with a high Ki-67 index and receipt of prior chemotherapy with cisplatin and irinotecan. Grade 3-4 neutropenia and anemia were observed in four and five patients, respectively. Conclusion. Amrubicin monotherapy appears to be potentially active and well-tolerated for platinum-refractory gastroenteropancreatic NEC.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Amrubicin monotherapy for patients with platinum-refractory gastroenteropancreatic neuroendocrine carcinoma.

Ando

Hosokawa

Yoshita

et al. 2015

JCO

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“…There are occasions when this rule does not apply. Several phase 2 studies have demonstrated that single-agent amrubicin (AMR) had promising effects on patients with refractory SCLC (31,32). Results from these studies showed overall response rates of 21.3 to 53% and median survival periods of 5.7 to 10.3 months in refractory SCLC.…”

Section: Treatmentsmentioning

confidence: 90%

Second-line chemotherapy for refractory small cell neuroendocrine carcinoma of the esophagus that relapsed after complete remission with irinotecan plus cisplatin therapy: Case report and review of the literature

et al. 2012

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Abstract. Small cell esophageal carcinoma is a type of small cell neuroendocrine carcinoma (SCNEC). SCNEC follows an aggressive clinical course and has a poor prognosis despite multidisciplinary therapies. A standard therapeutic strategy, including surgery, radiation and first-/second-line chemotherapy, has not yet been established for SCNEC. We present a case of SCNEC of the esophagus. A 66-year-old male with SCNEC as extensive disease was treated with 60 mg/m 2 cisplatin on day 1 plus 60 mg/m 2 irinotecan on days 1, 8 and 15 every 4 weeks (IP) with successful complete remission. After the sixth course of IP, increasing pro-gastrin-releasing peptide (ProGRP) and nonspecific enolase (NSE) levels and intense fluorodeoxyglucose (FDG) avidity in a lymph node around the celiac artery (SUV max , 8.3) indicated a refractory relapse of the disease. The patient was treated with three courses of amrubicin (AMR, 35 mg/m 2 ) administered intravenously for 3 consecutive days every 3 weeks as a second-line chemotherapy. The ProGRP and NSE levels returned to the normal range 1 month after the initiation of second-line chemotherapy. However, the ProGRP and NSE levels were elevated after the third course of AMR, and PET-CT revealed progressive disease with liver metastasis and extended lymph node metastasis. As the patient remained asymptomatic, paclitaxel (100 mg/m 2 ) was started as third-line chemotherapy. Patients with SCNEC of the esophagus with extensive disease should be treated with aggressive chemotherapy rather than surgery or radiation monotherapy. In the present case, tumor markers such as ProGRP and NSE were predictive of relapse and PET-CT was used to detect relapse. Further research is required to identify and exploit promising agents for resistant SCNEC.

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“…Grade 3-4 neutropenia, thrombopenia and anemia were seen in 84.8%, 39.4% and 78.8% respectively [Yana et al 2007]. While the antitumor activity of amrubicin was confirmed, more severe and frequent hematologic toxicities concerned clinicians compared with topotecan or irinotecan [Ettinger et al 2010]. Then, a variety of phase II trials have been conducted at different doses of amrubicin for relapsed SCLC as shown in Table 4.…”

Section: Cytotoxic Agentsmentioning

confidence: 99%

Relapsed small cell lung cancer: treatment options and latest developments

et al. 2014

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According to recent analyses, there was a modest yet significant improvement in median survival time and 5-year survival rate of limited stage small cell lung cancer (SCLC) in North America, Europe, Japan and other countries over the last 30 years. The median survival time of limited stage SCLC is 15-20 months and 5-year survival rate is 15% or less. In terms of extensive stage SCLC, a median survival time of 9.4-12.8 months and 2-year survival of 5.2-19.5% are still disappointing. Despite being highly sensitive to first-line chemotherapy and radiotherapy treatments, most patients with SCLC experience relapse within 2 years and die from systemic metastasis. While several clinical trials of cytotoxic chemotherapies and molecular targeting agents have been investigated in the treatment of relapsed SCLC, none showed a significant clinical activity to be able to exceed topotecan as second-line chemotherapy. There are problematic issues to address for relapsed SCLC, such as standardizing the treatment for third-line chemotherapy. Topotecan alone was the first approved therapy for second-line treatment for relapsed SCLC. Amrubicin is a promising drug and a variety of trials evaluating its efficacy have been carried out. Amrubicin has shown superiority to topotecan in a Japanese population, but was not superior in a study of western patients. There are some controversial issues for relapsed SCLC, such as treatment for older patients, third-line chemotherapy and efficacy of molecular targeting therapy. This article reviews current standard treatment, recent clinical trials and other topics on relapsed SCLC.

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Phase II Study of Amrubicin As Second-Line Therapy in Patients With Platinum-Refractory Small-Cell Lung Cancer

Abstract: Single-agent amrubicin showed promising activity with a 21.3% ORR and an acceptable safety profile when used as second-line therapy patients with platinum-refractory SCLC. Amrubicin did not induce early cardiotoxicity, but its long-term effects are unknown.

Cited by 115 publications

References 23 publications

Amrubicin monotherapy for patients with platinum-refractory gastroenteropancreatic neuroendocrine carcinoma.

Amrubicin monotherapy for patients with platinum-refractory gastroenteropancreatic neuroendocrine carcinoma.

Second-line chemotherapy for refractory small cell neuroendocrine carcinoma of the esophagus that relapsed after complete remission with irinotecan plus cisplatin therapy: Case report and review of the literature

Relapsed small cell lung cancer: treatment options and latest developments

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