Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer

Kim, Dong Wan; Kim, Hoon Gu; Kim, Joo Hang; Park, Keunchil; Kim, Hoon Kyo; Jang, Joung Soon; Kim, Bong Seog; Kang, Jin Hyoung; Lee, Kyung Hee; Kim, Sang We; Ryoo, Hun Mo; Lee, Ki Hyeong; Kwon, Jung Hye; Choi, Jin Hyuk; Shin, Sang Won; Hahn, Seokyung; Heo, Dae Seog

doi:10.4143/crt.2018.019

Cited by 28 publications

(39 citation statements)

References 22 publications

(18 reference statements)

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“…In 2002, a randomized phase 3 trial (Japanese Clinical Oncology Group 9511) demonstrated better response and survival in patients with extensive‐stage SCLC who were treated with irinotecan and cisplatin (IP regimen) compared with those treated with EP . A recent Korean study also demonstrated no significant differences in overall survival (OS) and progression‐free survival (PFS) between the IP and EP treatment arms for SCLC . Furthermore, a large Japanese, retrospective, multicenter study of patients with advanced NEC of the digestive system reported a higher response rate (RR) and survival among those treated with IP (160 patients) compared with EP (46 patients) (RR: 50% vs 28%; OS: 13.0 months vs 7.3 months) .…”

Section: Introductionmentioning

confidence: 99%

Etoposide and cisplatin versus irinotecan and cisplatin as the first‐line therapy for patients with advanced, poorly differentiated gastroenteropancreatic neuroendocrine carcinoma: A randomized phase 2 study

Zhang

et al. 2020

Cancer

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BACKGROUND: Platinum-based chemotherapy is recommended for the treatment of advanced gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC). The objective of the current phase 2 study was to compare the efficacy and toxicity between etoposide and cisplatin (EP) and irinotecan and cisplatin (IP) as first-line treatment in patients with advanced GEP-NEC. METHODS: Patients with advanced, poorly differentiated GEP-NEC randomly were assigned to receive EP or IP. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival, overall survival, and toxicities. RESULTS: The planned size of the study population was 144 patients, but enrollment was terminated early at 66 patients because the premature analysis found similar responses in the 2 treatment arms. The ORRs of the EP and IP arms both were 42.4% (14 of 33 patients). The efficacy was similar for small cell NEC with EP or IP (63.2% and 61.5%, respectively; P = .61), whereas that of IP was slightly better in patients with non-small cell NEC (30% vs 14.3%; P = .42). The median progression-free survival was 6.4 months and 5.8 months, respectively, for the EP and IP arms (P = .81), and the median overall survival was 11.3 months and 10.2 months, respectively, for the EP and IP arms (P = .37). The incidence of grade 3/4 neutropenia was significantly higher in the EP arm compared with the IP arm (45.4% vs 12.1%; P = .002). Nonhematological toxicity was relatively mild and more frequent in the IP arm compared with the EP arm (54.5% vs 18.2%; P = .001). No toxicity-related deaths were reported. CONCLUSIONS: The results of the current study demonstrated that IP is not inferior to EP, with comparable efficacy for poorly differentiated NEC of the digestive system. In addition, both regimens appear to be well tolerated with diverse toxicity profiles.

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Section: Introductionmentioning

confidence: 99%

Etoposide and cisplatin versus irinotecan and cisplatin as the first‐line therapy for patients with advanced, poorly differentiated gastroenteropancreatic neuroendocrine carcinoma: A randomized phase 2 study

Zhang

et al. 2020

Cancer

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“…T‐AML caused by alkylating agents and radiotherapy usually develops 5‐7 years after therapy and is characterized by monosomy . On the other hand, t‐AML caused by topoisomerase α inhibitors occurs typically 1‐3 years after therapy and is characterised by the chromosomal abnormalities 11q23 and 21q22 . Because of the long‐term administration of topoisomerase II inhibitors and the timing of the onset, t‐AML in our case was classified as t‐AML caused by topoisomerase II inhibitors.…”

Section: Discussionmentioning

confidence: 86%

“…3,4,7,9 On the other hand, t-AML caused by topoisomerase α inhibitors occurs typically 1-3 years after therapy and is characterised by the chromosomal abnormalities 11q23 and 21q22. 4,5 Because of the long-term administration of topoisomerase II inhibitors and the timing of the onset, t-AML in our case was classified as t-AML caused by topoisomerase II inhibitors. Although t-AML caused by topoisomerase II inhibitors usually exhibits 11q23 and 21q22, our case showed atypical monosomy 7 and trisomy 8 chromosomal abnormalities.…”

Section: Discussionmentioning

confidence: 97%

“…This case highlights two important clinical issues. First, t‐AML can occur during the treatment for ED‐SCLC which has a poor prognosisand usually cannot survive until developing hematological malignancy (median survival of 8‐13 months and <5% of patients surviving >2 years) . T‐AML is common in hematological malignancies and breast cancer .…”

Section: Discussionmentioning

confidence: 99%

“…First, t-AML can occur during the treatment for ED-SCLC which has a poor prognosisand usually cannot survive until developing hematological malignancy (median survival of 8-13 months and <5% of patients surviving >2 years). 5 T-AML is common in hematological malignancies and breast cancer. 1 The onset of t-AML caused by topoisomerase II inhibitors is often delayed by 2-3 years, and at a total dose of 2000 mg/m 2 or more the incidence increases from 0.5% to 2.6%.…”

Section: Discussionmentioning

confidence: 99%

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Therapy‐related acute myeloid leukemia after chemotherapy in extensive disease‐small cell lung cancer

Ueda

Fujita

Okuno

et al. 2018

Clinical Case Reports

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Key Clinical MessageWe experienced therapy‐related acute myeloid leukemia (t‐AML) in a patient with extensive disease‐small cell lung cancer (ED‐SCLC). This case is rare and has educational message because ED‐SCLC has a poor prognosis and often cannot survive until developing therapy related hematological malignancy. Furthermore this case had unique chromosomal abnormalities. With recent advances in chemotherapy and radiotherapy, the prognosis of lung cancer has improved, while t‐AML has been increasing in frequency.

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Comparison of First-Line Treatments for Patients With Extensive-Stage Small Cell Lung Cancer

et al. 2020

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IMPORTANCE Combinations of chemotherapy with immunotherapy or bevacizumab in first-line treatments of extensive-stage small cell lung cancer (ES-SCLC) have been evaluated in various clinical trials. However, it remains unclear what the optimal combination regimen is. OBJECTIVE To clarify which first-line combination regimen is associated with the best tumor response among patients with ES-SCLC. DATA SOURCES Electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) were systematically searched to extract eligible literature from database inception to December 2019. STUDY SELECTION Head-to-head randomized clinical trials on first-line treatments for patients with ES-SCLC were included with outcomes and toxic effects reported, including objective response rate (ORR, involving complete response and partial response), disease control rate (DCR, involving complete response, partial response, and stable disease), progression-free survival (PFS), overall survival (OS), and treatment related adverse events (TRAEs) of grades 3 to 5. Of 199 eligible articles, 14 were included. DATA EXTRACTION AND SYNTHESIS Data were independently extracted and collected by 2 reviewers based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES Main outcomes were OS, PFS, DCR, ORR, and TRAEs of grades 3 to 5. RESULTS A total of 3 phase 2 and 11 phase 3 randomized clinical trials involving 4838 patients were included. Programmed cell death ligand 1 (PD-L1) inhibitor (durvalumab and atezolizumab) plus etoposide-based chemotherapy, compared with etoposide-based chemotherapy alone, showed the most favorable OS (hazard ratio, 1.40; 95% CI, 1.09-1.80) and the best DCR (odds ratio [OR], 0.42; 95% CI, 0.21-0.81). Bevacizumab plus etoposide-based chemotherapy provided the best PFS compared with etoposide-based chemotherapy alone (hazard ratio, 1.54; 95% CI, 1.09-2.27), although this was not translated into OS benefit. The addition of PD-L1 inhibitors to etoposideplatinum chemotherapy caused no more toxic effects in general (compared with etoposide-based chemotherapy alone: OR, 1.14; 95% CI, 0.36-2.31), while bevacizumab plus etoposide-platinum regimen induced the most TRAEs grades 3 to 5 among all first-line treatments (eg, compared with irinotecan-platinum regimen: OR, 4.24; 95% CI, 1.26-14.57). Based on the surface under the (continued) Key Points Question Is the combination of a programmed cell death ligand 1 (PD-L1) inhibitor with etoposide-platinum chemotherapy associated with better tumor response among patients with extensive-stage small cell lung cancer compared with other first-line treatments? Findings In this systematic review and network meta-analysis of 3 phase 2 and 11 phase 3 randomized clinical trials, which included 4838 patients, the combination of a PD-L1 inhibitor (durvalumab or atezolizumab) with etoposide-platinum regimen was associated with better tumor response and sa...

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Randomized Phase III Trial of Irinotecan Plus Cisplatin versus Etoposide Plus Cisplatin in Chemotherapy-Naïve Korean Patients with Extensive-Disease Small Cell Lung Cancer

Abstract: The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC. (ClinicalTrials.gov Identifier: NCT00349492).

Cited by 28 publications

References 22 publications

Etoposide and cisplatin versus irinotecan and cisplatin as the first‐line therapy for patients with advanced, poorly differentiated gastroenteropancreatic neuroendocrine carcinoma: A randomized phase 2 study

Etoposide and cisplatin versus irinotecan and cisplatin as the first‐line therapy for patients with advanced, poorly differentiated gastroenteropancreatic neuroendocrine carcinoma: A randomized phase 2 study

Therapy‐related acute myeloid leukemia after chemotherapy in extensive disease‐small cell lung cancer

Comparison of First-Line Treatments for Patients With Extensive-Stage Small Cell Lung Cancer

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