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Published in: Cancer Chemotherapy and Pharmacology 4/2015

01-04-2015 | Original Article

Amrubicin monotherapy for patients with extrapulmonary neuroendocrine carcinoma after platinum-based chemotherapy

Authors: Kenta Nio, Shuji Arita, Taichi Isobe, Hitoshi Kusaba, Kenichi Kohashi, Tatsuhiro Kajitani, Shingo Tamura, Gen Hirano, Kenji Mitsugi, Akitaka Makiyama, Taito Esaki, Hiroshi Ariyama, Yoshinao Oda, Koichi Akashi, Eishi Baba

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015

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Abstract

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/m2/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.
Literature
1.
go back to reference Bosman FT, Carbeuri F, Hruban RH, Theise ND (2010) WHO classification of tumors of the digestive system, 4th edn. WHO Press, Geneva, pp 13–14 Bosman FT, Carbeuri F, Hruban RH, Theise ND (2010) WHO classification of tumors of the digestive system, 4th edn. WHO Press, Geneva, pp 13–14
2.
go back to reference Brenner B, Tang LH, Shia J, Klimstra DS, Kelsen DP (2007) Small cell carcinomas of the gastrointestinal tract: clinicopathological features and treatment approach. Semin Oncol 34:43–50CrossRefPubMed Brenner B, Tang LH, Shia J, Klimstra DS, Kelsen DP (2007) Small cell carcinomas of the gastrointestinal tract: clinicopathological features and treatment approach. Semin Oncol 34:43–50CrossRefPubMed
3.
go back to reference Sundstrom S, Bremnes RM, Kaasa S et al (2002) Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years follow-up. J Clin Oncol 20:4665–4672CrossRefPubMed Sundstrom S, Bremnes RM, Kaasa S et al (2002) Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years follow-up. J Clin Oncol 20:4665–4672CrossRefPubMed
4.
go back to reference Noda K, Nishiwaki Y, Kawahara M et al (2002) Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346:85–91CrossRefPubMed Noda K, Nishiwaki Y, Kawahara M et al (2002) Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 346:85–91CrossRefPubMed
5.
go back to reference von Pawel J, Schiller JH, Shepherd FA et al (1999) Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17:658–667 von Pawel J, Schiller JH, Shepherd FA et al (1999) Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17:658–667
6.
go back to reference O’Brien ME, Ciuleanu TE, Tsekov H et al (2006) Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 24:5441–5447CrossRefPubMed O’Brien ME, Ciuleanu TE, Tsekov H et al (2006) Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 24:5441–5447CrossRefPubMed
7.
go back to reference Inoue A, Sugawara S, Yamazaki K et al (2008) Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402. J Clin Oncol 26:5401–5406CrossRefPubMed Inoue A, Sugawara S, Yamazaki K et al (2008) Randomized phase II trial comparing amrubicin with topotecan in patients with previously treated small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0402. J Clin Oncol 26:5401–5406CrossRefPubMed
8.
go back to reference von Pawel J, Ardizzoni A, Thatcher N (2003) The relationship between treatment-free interval (TFI) and outcomes to therapy in patients with relapsed small cell lung cancer (SCLC): a review of 631 patients treated with iv topotecan in 6 studies. Lung Cancer 41(Suppl. 2):S235CrossRef von Pawel J, Ardizzoni A, Thatcher N (2003) The relationship between treatment-free interval (TFI) and outcomes to therapy in patients with relapsed small cell lung cancer (SCLC): a review of 631 patients treated with iv topotecan in 6 studies. Lung Cancer 41(Suppl. 2):S235CrossRef
10.
go back to reference Maru DM, Khurana H, Rashid A et al (2008) Retrospective study of clinicopathologic features and prognosis of high-grade neuroendocrine carcinoma of the esophagus. Am J Surg Pathol 32:1404–1411CrossRefPubMed Maru DM, Khurana H, Rashid A et al (2008) Retrospective study of clinicopathologic features and prognosis of high-grade neuroendocrine carcinoma of the esophagus. Am J Surg Pathol 32:1404–1411CrossRefPubMed
11.
go back to reference Mitry E, Baudin E, Ducreux M et al (1999) Treatment of poorly differentiated neuroendocrine tumors with etoposide and cisplatin. Br J Cancer 81:1351–1355CrossRefPubMedCentralPubMed Mitry E, Baudin E, Ducreux M et al (1999) Treatment of poorly differentiated neuroendocrine tumors with etoposide and cisplatin. Br J Cancer 81:1351–1355CrossRefPubMedCentralPubMed
12.
go back to reference Mangum MD, Greco FA, Hainsworth JD, Hande KR, Johnson DH (1989) Combined small-cell and non-small-cell lung cancer. J Clin Oncol 7:607–612PubMed Mangum MD, Greco FA, Hainsworth JD, Hande KR, Johnson DH (1989) Combined small-cell and non-small-cell lung cancer. J Clin Oncol 7:607–612PubMed
13.
go back to reference Matsui K, Kitagawa M, Miwa A, Kuroda Y, Tsuji M (1991) Small cell carcinoma of the stomach: a clinicopathologic study of 17 cases. Am J Gastroenterol 86:1167–1175PubMed Matsui K, Kitagawa M, Miwa A, Kuroda Y, Tsuji M (1991) Small cell carcinoma of the stomach: a clinicopathologic study of 17 cases. Am J Gastroenterol 86:1167–1175PubMed
14.
go back to reference NCCN lung 2014: NCCN Clinical Practice Guidelines in Oncology, Neuroendocrine Tumors, version 2.2014 (HGNET1) NCCN lung 2014: NCCN Clinical Practice Guidelines in Oncology, Neuroendocrine Tumors, version 2.2014 (HGNET1)
15.
go back to reference Ettinger DS, Jotte R, Lorigan P et al (2010) Phase II study of amrubicin as second-line therapy in patients with platinum-refractory small-cell lung cancer. J Clin Oncol 28:2598–2603CrossRefPubMed Ettinger DS, Jotte R, Lorigan P et al (2010) Phase II study of amrubicin as second-line therapy in patients with platinum-refractory small-cell lung cancer. J Clin Oncol 28:2598–2603CrossRefPubMed
16.
go back to reference von Pawel J, Jotte R, Spigel DR et al (2014) Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol 32:4012–4020CrossRef von Pawel J, Jotte R, Spigel DR et al (2014) Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol 32:4012–4020CrossRef
17.
go back to reference Murakami H, Yamamoto N, Shibata T et al (2014) A single-arm confirmatory study of amrubicin therapy in patients with refractory small-cell lung cancer: Japan Clinical Oncology Group Study (JCOG0901). Lung Cancer 84:67–72CrossRefPubMed Murakami H, Yamamoto N, Shibata T et al (2014) A single-arm confirmatory study of amrubicin therapy in patients with refractory small-cell lung cancer: Japan Clinical Oncology Group Study (JCOG0901). Lung Cancer 84:67–72CrossRefPubMed
18.
go back to reference Asayama M, Fuse N, Yoshino Y et al (2011) Amrubicin for the treatment of neuroendocrine carcinoma of the gastrointestinal tract: a retrospective analysis of five cases. Cancer Chemother Pharmacol 68:1325–1330CrossRefPubMed Asayama M, Fuse N, Yoshino Y et al (2011) Amrubicin for the treatment of neuroendocrine carcinoma of the gastrointestinal tract: a retrospective analysis of five cases. Cancer Chemother Pharmacol 68:1325–1330CrossRefPubMed
19.
go back to reference Eckardt JR, von Pawel J, Pujol JL et al (2007) Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 25:2086–2092CrossRefPubMed Eckardt JR, von Pawel J, Pujol JL et al (2007) Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 25:2086–2092CrossRefPubMed
20.
go back to reference Sugimoto Y, Tsukahara S, Oh-hara T, Liu LF, Tsuruo T (1990) Elevated expression of DNA topoisomerase II in camptothecin-resistant human tumor cell-lines. Cancer Res 50:7962–7965PubMed Sugimoto Y, Tsukahara S, Oh-hara T, Liu LF, Tsuruo T (1990) Elevated expression of DNA topoisomerase II in camptothecin-resistant human tumor cell-lines. Cancer Res 50:7962–7965PubMed
Metadata
Title
Amrubicin monotherapy for patients with extrapulmonary neuroendocrine carcinoma after platinum-based chemotherapy
Authors
Kenta Nio
Shuji Arita
Taichi Isobe
Hitoshi Kusaba
Kenichi Kohashi
Tatsuhiro Kajitani
Shingo Tamura
Gen Hirano
Kenji Mitsugi
Akitaka Makiyama
Taito Esaki
Hiroshi Ariyama
Yoshinao Oda
Koichi Akashi
Eishi Baba
Publication date
01-04-2015
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-015-2706-y

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