Phase II clinical trial of metronomic chemotherapy with combined irinotecan and tegafur–gimeracil–oteracil potassium in metastatic and recurrent breast cancer

Otsuka, Hiroko; Fujii, Teruhiko; Toh, Uhi; Iwakuma, Nobutaka; Takahashi, Ryuji; Mishima, Mai; Takenaka, Miki; Kakuma, Tatsuyuki; Tanaka, Maki; Shirouzu, Kazuo

doi:10.1007/s12282-013-0483-1

Cited by 20 publications

(14 citation statements)

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“…Munzone et al summarized some ongoing clinical trials and the forthcoming results may be helpful [2,15]. Meanwhile, according to the principles of precision medicine, prognosis factors such as vascular endothelial growth factor (VEGF), serum HER-2 and EGFR, endothelial nitric oxide synthase (eNOS), thrombospondin-1 (THBS-1), circulating endothelial cells (CECs), and gene polymorphism should be considered for patient selection to standardize MCT [18,26,28,32,43]. …”

Section: Discussionmentioning

confidence: 99%

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

Liu

Liang

et al. 2017

PLoS ONE

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PurposeThe current meta-analysis aimed to summarize the available evidence for the efficacy and serious adverse events (AEs) associated with use of metronomic chemotherapy (MCT) in patients with metastatic breast cancer (MBC).MethodElectronic databases (PubMed, EMBASE database, Web of Knowledge, and the Cochrane database) were systematically searched for articles related to the use of MCT in MBC patients. Eligible studies included clinical trials of MBC patients treated with MCT that presented sufficient data related to tumor response, progression-free survival (PFS), overall survival (OS), and grade 3/4 AEs. A meta-analysis was performed using a random effects model.ResultsThis meta-analysis consists of 22 clinical trials with 1360 patients. The pooled objective response rate and clinical benefit rate of MCT were 34.1% (95% CI 27.4–41.5) and 55.6% (95% CI 49.2–61.9), respectively. The overall 6-month PFS, 12-month OS, and 24-month OS rates were 56.8% (95% CI 48.3–64.9), 70.3% (95% CI 62.6–76.9), and 40.0% (95% CI 30.6–50.2), respectively. The pooled incidence of grade 3/4 AEs was 29.5% (95% CI 21.1–39.5). There was no statistically significant difference observed in any endpoint between subgroups defined by concomitant anti-cancer therapies or chemotherapy regimens. After excluding one controversial study, we observed a trend showing lower toxicity rates with the use of MCT alone compared to use of MCT with other anti-cancer therapies (P = 0.070).ConclusionsMetronomic chemotherapy may be effective for use in patients with metastatic breast cancer. MCT used alone is possibly equally effective and less toxic than combination therapies. Well-designed RCTs are needed to obtain more evidence.

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Section: Discussionmentioning

confidence: 99%

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

Liu

Liang

et al. 2017

PLoS ONE

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“…Via steps of screening the title and reading the abstract, 5 studies were identified (Frasci et al, 2005;Stathopoulos et al, 2005;Moulder et al, 2008;Lee et al, 2013;Otsuka, et al, 2013). These studies had been carried out in China, Japan, Korea, Europe and the USA.…”

Section: Resultsmentioning

confidence: 99%

“…When irinotecan is used for treating patients with MBC, several studies should be mentioned. One is a Japanese study comprised 40 patients aged 35-79 years (Otsuka et al, 2013). In this study, Irinotecan was administered at 60 mg/m 2 , and was infused on days 1, 8, and 15 for every 4 weeks, and accompanied by TS-1 (at 80 mg/m 2 /day orally on days 3-7, 10-14, and 17-21 every 4 weeks) (Otsuka et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, Irinotecan was administered at 60 mg/m 2 , and was infused on days 1, 8, and 15 for every 4 weeks, and accompanied by TS-1 (at 80 mg/m 2 /day orally on days 3-7, 10-14, and 17-21 every 4 weeks) (Otsuka et al, 2013). As results of this study, among 34 patients whose tumor response data were available, the response rate was 47% (1 complete and 15 partial responses); stable disease was observed in 17 patients (50%); one patient had disease progression (3%); median progression-free survival was 14 months; median overall survival was 26 months, and 79.3% of patients survived for 1 year; the most common grade 3 or 4 adverse events were neutropenia, leukopenia, diarrhea, and anemia (Otsuka et al, 2013). However, the response rate is lower in a study conducted in the USA (Moulder et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

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Irinotecan as a Palliative Therapy for Metastatic Breast Cancer Patients after Previous Chemotherapy

Lan¹,

Li²,

Lin³

2015

Asian Pacific Journal of Cancer Prevention

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Background: This analysis was conducted to evaluate the efficacy and safety of irinotecan based chemotherapy for treatment of patients with metastatic breast cancer (MBC) who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline-or taxane-based. Methods: Clinical studies were identified using a predefined search strategy. Pooled response rates (RR) to treatment were calculated. Results: As irinotecan based regimens, 5 clinical studies which including 217 patients with refractory MBC were considered eligible for inclusion, with irinotecan, cisplatin, capecitabine, or TS-1. Systemic analysis suggested that, in all patients, pooled RR was 48.8% (106/217) with irinotecan based regimens. Thrombocytopenia and leukocytopenia were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related deaths occurred. Conclusion: This systemic analysis suggests that irinotecan based regimens are beneficial and safe for treating patients with MBC after other chemotherapy.

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“…Irinotecan (CPT-11), a water-soluble derivative of camptothecin, is a highly effective chemotherapeutic agent which has been widely used in clinical practice to treat colon (Mukai et al, 2009), gastric (Takiuchi, 2009), pancreatic (Stathopoulos et al, 2003), and varieties of other cancers (Mrozek et al, 2008; Otsuka et al, 2015; Trafalis et al, 2016) through the inhibition of DNA topoisomerase I. However, dose-limiting toxicities myelosuppression, neutropenia, and gastrointestinal (GI) toxicity, particularly severe late-onset diarrhea, compromise the efficacy and safety of irinotecan-based chemotherapy (Kakolyris et al, 2001; Benson et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

HuangQin Decoction Attenuates CPT-11-Induced Gastrointestinal Toxicity by Regulating Bile Acids Metabolism Homeostasis

et al. 2017

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Irinotecan (CPT-11) is a potent chemotherapeutic agent, however, its clinical usage is often limited by the induction of severe gastrointestinal (GI) toxicity, especially late-onset diarrhea. HuangQin Decoction (HQD), commonly used for the treatment of GI ailments, has been proved could significantly ameliorate the intestinal toxicity of CPT-11. To reveal the mechanisms of CPT-11-induced toxicity and the modulation effects of HQD, a previous untargeted metabolomics study was performed and the results indicated that HQD may protect the GI tract by altering the metabolism of bile acids (BAs). Nevertheless, the untargeted assays are often less sensitive and/or efficient. In order to further confirm our previous findings, here in this paper, serum and tissues metabolic profiles of 17 BAs were analyzed using liquid chromatography-tandem mass spectrometry based targeted metabolomics. The results indicated that serum and tissues levels of most BAs were significantly decreased after CPT-11 administration, except some hydrophobic BAs. Co-treatment with HQD could markedly attenuate CPT-11-induced GI toxicity and reverse the alterations of hydrophobic BAs. Despite the fact that the BAs pool size remained unchanged, the balance of BAs had shifted leading to decreased toxicity after HQD treatment. The present study demonstrated for the first time that the precise interaction between HQD, CPT-11-induced intestinal toxicity and BAs’ homeostasis.

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Phase II clinical trial of metronomic chemotherapy with combined irinotecan and tegafur–gimeracil–oteracil potassium in metastatic and recurrent breast cancer

Abstract: Metronomic chemotherapy with combined irinotecan and TS-1 was effective in MRBC patients. Adverse effects were mild and the regimen was safely administered without identifying UGT1A1 polymorphisms.

Cited by 20 publications

References 34 publications

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

Irinotecan as a Palliative Therapy for Metastatic Breast Cancer Patients after Previous Chemotherapy

HuangQin Decoction Attenuates CPT-11-Induced Gastrointestinal Toxicity by Regulating Bile Acids Metabolism Homeostasis

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