Skip to main content
Erschienen in: Gastric Cancer 3/2018

01.05.2018 | Original Article

Irinotecan monotherapy as third-line or later treatment in advanced gastric cancer

verfasst von: Akitaka Makiyama, Kohei Arimizu, Gen Hirano, Chinatsu Makiyama, Yuzo Matsushita, Tsuyoshi Shirakawa, Hirofumi Ohmura, Masato Komoda, Keita Uchino, Kyoko Inadomi, Shuji Arita, Hiroshi Ariyama, Hitoshi Kusaba, Yudai Shinohara, Miyuki Kuwayama, Tatsuhiro Kajitani, Hisanobu Oda, Taito Esaki, Koichi Akashi, Eishi Baba

Erschienen in: Gastric Cancer | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

Patients with advanced gastric cancer (AGC) are often treated with irinotecan monotherapy as salvage-line therapy. However, the survival benefit of this therapy remains to be elucidated.

Methods

Medical records of AGC patients who were treated with irinotecan monotherapy as salvage-line treatment in six institutions from 2007 to 2014 were reviewed.

Results

A total of 146 patients had prior fluoropyrimidine and taxane therapies, and 75.3% had prior platinum therapy. The median age was 66 (range 27–81) years, and 102 males (69.9%) were included. Performance status (PS) was 0/1/2/3 in 53/70/19/4 patients. Eighty-nine patients (61.0%) had two or more metastatic sites. Irinotecan monotherapy as 3rd-/4th-line therapy was performed in 135/11 (92.5%/7.5%). The median number of administrations was 4 (range 1–62). Forty-six patients (31.5%) required initial dose reduction at the physician’s discretion. The overall response rate was 6.8%, and the disease control rate was 43.1%. The median PFS was 3.19 months [95% confidence interval (CI) 2.30–4.08 months], and the median OS was 6.61 months (95% CI 5.94–7.28 months). Grade 3/4 adverse events were hematological toxicity (46 patients, 31.5%) and non-hematological toxicity (50 patients, 34.2%). Hospitalization due to adverse events was required in 31 patients (21.2%). Patients with relative dose intensity (RDI) less than 80% showed similar survival to those with RDI 80% or higher.

Conclusions

Irinotecan monotherapy was relatively safely performed as salvage-line treatment for AGC in Japanese clinical practice. Careful patient selection and intensive modification of the dose of irinotecan might possibly be associated with favorable survival.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
2.
Zurück zum Zitat Association Japanese Gastric Cancer. Japanese gastric cancer treatment guidelines 2014 (ver.4). Gastric Cancer. 2017;20:1–19.CrossRef Association Japanese Gastric Cancer. Japanese gastric cancer treatment guidelines 2014 (ver.4). Gastric Cancer. 2017;20:1–19.CrossRef
3.
Zurück zum Zitat Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–21.CrossRefPubMed Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–21.CrossRefPubMed
4.
Zurück zum Zitat Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009;10:1063–9.CrossRefPubMed Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009;10:1063–9.CrossRefPubMed
5.
Zurück zum Zitat Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009;20:666–73.CrossRefPubMed Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009;20:666–73.CrossRefPubMed
6.
Zurück zum Zitat Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46.CrossRefPubMed Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46.CrossRefPubMed
7.
Zurück zum Zitat Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRefPubMed Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRefPubMed
8.
Zurück zum Zitat Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, et al. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer—a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011;47:2306–14.CrossRefPubMed Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, et al. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer—a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011;47:2306–14.CrossRefPubMed
9.
Zurück zum Zitat Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, et al. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012;30:1513–8.CrossRefPubMed Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, et al. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012;30:1513–8.CrossRefPubMed
10.
Zurück zum Zitat Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014;15:78–86.CrossRefPubMed Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014;15:78–86.CrossRefPubMed
11.
Zurück zum Zitat Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–9.CrossRefPubMed Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–9.CrossRefPubMed
12.
Zurück zum Zitat Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.CrossRefPubMed Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.CrossRefPubMed
13.
Zurück zum Zitat Rothenberg ML. CPT-11: an original spectrum of clinical activity. Semin Oncol. 1996;23:21–6.PubMed Rothenberg ML. CPT-11: an original spectrum of clinical activity. Semin Oncol. 1996;23:21–6.PubMed
14.
Zurück zum Zitat Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, et al. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013;31:4438–44.CrossRefPubMed Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, et al. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013;31:4438–44.CrossRefPubMed
15.
Zurück zum Zitat Shitara K, Matsuo K, Mizota A, Kondo C, Nomura M, Takahari D, et al. Association of fluoropyrimidines, platinum agents, taxanes, and irinotecan in any line of chemotherapy with survival in patients with advanced gastric cancer. Gastric Cancer. 2011;14:155–60.CrossRefPubMed Shitara K, Matsuo K, Mizota A, Kondo C, Nomura M, Takahari D, et al. Association of fluoropyrimidines, platinum agents, taxanes, and irinotecan in any line of chemotherapy with survival in patients with advanced gastric cancer. Gastric Cancer. 2011;14:155–60.CrossRefPubMed
16.
Zurück zum Zitat Kawakami T, Machida N, Yasui H, Kawahira M, Kawai S, Kito Y, et al. Efficacy and safety of irinotecan monotherapy as third-line treatment for advanced gastric cancer. Cancer Chemother Pharmacol. 2016;78:809–14.CrossRefPubMed Kawakami T, Machida N, Yasui H, Kawahira M, Kawai S, Kito Y, et al. Efficacy and safety of irinotecan monotherapy as third-line treatment for advanced gastric cancer. Cancer Chemother Pharmacol. 2016;78:809–14.CrossRefPubMed
17.
Zurück zum Zitat Kang YK, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, et al. Nivolumab (ONO-4538/BMS-936558) as salvage treatment after second or later-line chemotherapy for advanced gastric or gastro-esophageal junction cancer (AGC): A double-blinded, randomized, phase III trial. J Clin Oncol 35, 2017 (suppl 4S; abstract 2). Kang YK, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, et al. Nivolumab (ONO-4538/BMS-936558) as salvage treatment after second or later-line chemotherapy for advanced gastric or gastro-esophageal junction cancer (AGC): A double-blinded, randomized, phase III trial. J Clin Oncol 35, 2017 (suppl 4S; abstract 2).
18.
Zurück zum Zitat Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, et al. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer. 2014;50:1437–45.CrossRefPubMed Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, et al. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer. 2014;50:1437–45.CrossRefPubMed
19.
Zurück zum Zitat Nishimura T, Iwasa S, Nagashima K, Okita N, Takashima A, Honma Y, et al. Irinotecan monotherapy as third-line treatment for advanced gastric cancer refractory to fluoropyrimidines, platinum, and taxanes. Gastric Cancer. 2016 [Epub ahead of print]. Nishimura T, Iwasa S, Nagashima K, Okita N, Takashima A, Honma Y, et al. Irinotecan monotherapy as third-line treatment for advanced gastric cancer refractory to fluoropyrimidines, platinum, and taxanes. Gastric Cancer. 2016 [Epub ahead of print].
Metadaten
Titel
Irinotecan monotherapy as third-line or later treatment in advanced gastric cancer
verfasst von
Akitaka Makiyama
Kohei Arimizu
Gen Hirano
Chinatsu Makiyama
Yuzo Matsushita
Tsuyoshi Shirakawa
Hirofumi Ohmura
Masato Komoda
Keita Uchino
Kyoko Inadomi
Shuji Arita
Hiroshi Ariyama
Hitoshi Kusaba
Yudai Shinohara
Miyuki Kuwayama
Tatsuhiro Kajitani
Hisanobu Oda
Taito Esaki
Koichi Akashi
Eishi Baba
Publikationsdatum
01.05.2018
Verlag
Springer Japan
Erschienen in
Gastric Cancer / Ausgabe 3/2018
Print ISSN: 1436-3291
Elektronische ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-017-0759-9

Weitere Artikel der Ausgabe 3/2018

Gastric Cancer 3/2018 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

CME: 2 Punkte

Prof. Dr. med. Gregor Antoniadis Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

CME: 2 Punkte

Dr. med. Benjamin Meyknecht, PD Dr. med. Oliver Pieske Das Webinar S2e-Leitlinie „Distale Radiusfraktur“ beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

CME: 2 Punkte

Dr. med. Mihailo Andric
Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.