Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer

Yamada, Suguru; Fujii, Tsutomu; Yokoyama, Yukihiro; Kawashima, Hiroki; Maeda, Osamu; Suzuki, Kôjiro; Okada, Tohru; Ono, E; Yamaguchi, Junpei; Takano, Nao; Takami, Hideki; Hayashi, Masamichi; Niwa, Yasumasa; Hirooka, Yoshiki; Ito, Yoshiyuki; Naganawa, Shinji; Ando, Yumiko; Nagino, Masato; Goto, Hidemi; Kodera, Yasuhiro

doi:10.1007/s00280-018-3554-3

Cited by 22 publications

(23 citation statements)

References 21 publications

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“…The front-line therapeutic options for LAPC patients are chemotherapy and radiotherapy, by which survival benefit is limited, and complications and adverse events (AEs) are frequent. Although some newer chemotherapy regimens like gemcitabine plus nab-paclitaxel, 5 dasatinib plus gemcitabine, 6 FOLFOX-6 7 , 8 and FOLFIRINOX 9 – 11 appear and have shown a substantial survival benefit in patients with LAPC, the long-term prognosis is still poor and the heterogeneity between these studies is significant. 12 Therefore, an optimal treatment for LAPC patients should provide survival benefit, alleviate pain, improve quality of life, but not cause severe compactions.…”

Section: Introductionmentioning

confidence: 99%

Response of patients with locally advanced pancreatic adenocarcinoma to high-intensity focused ultrasound treatment: a single-center, prospective, case series in China

Zhu

et al. 2018

CMAR

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PurposePatients with unresectable locally advanced pancreatic cancer (LAPC) are still in dire need of effective therapies. We performed this cohort study in order to assess the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in treating patients with unresectable LAPC.Patients and methodsEighty-seven cases with unresectable LAPC from January 2014 to December 2016 were finally recruited according to the inclusion criteria. The primary end point of our study was OS of all the cases, and the secondary end points included 6-month and 12-month survival rate, tumor response rate, carbohydrate antigen (CA) 19-9 response rate, VAS, quality of life, and safety.ResultsAll the 87 patients received HIFU ablation successfully, and were included in the efficacy and safety analysis. With a median follow-up of 16 months, median OS was estimated to be 12.2 months, with 95 % CI of 11.1–12.7 months. The 6-month and 12-month survival rates were 94.25% (95% CI =86.74–97.57) and 50.85% (95% CI =38.17–62.21), respectively. Multivariate analysis revealed that patients with VAS <4, Karnofsky performance status ≥80, and tumor size <3 cm have a significant improvement in their OS (adjusted HR [aHR] =0.26 [95% CI =0.12–0.57], P=0.001; aHR =0.34 [95% CI =0.17–0.68], P=0.02; and aHR =0.39 [95% CI =0.20–0.78], P=0.007; respectively). Tumor responses were observed in 32 (36.8%) of 87 patients and CA 19-9 response rate was 56.2%. Global health status, physical function, emotional function, and cognitive function of patients were significantly improved after HIFU treatment, and symptoms of fatigue and pain were significantly reduced. A total of 28.7% (25/87) of patients reported adverse events (AEs), mainly including fatigue (14/87), abdominal pain (7/87), fever (7/87), nausea (5/87), and rash (4/87). No severe AEs and HIFU-related deaths were reported.ConclusionHIFU ablation might be a potentially effective and safe therapeutic option for the patients with unresectable LAPC.

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Section: Introductionmentioning

confidence: 99%

Response of patients with locally advanced pancreatic adenocarcinoma to high-intensity focused ultrasound treatment: a single-center, prospective, case series in China

Zhu

et al. 2018

CMAR

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“…This trend is attributed largely to the current NCCN guidelines , and increasing evidence of the safety and efficacy of this treatment strategy has been reported . Also, CS for unresectable disease has been attempted because of recent advances in novel chemotherapy or chemoradiotherapy . In these situations, prolonged chemotherapy or chemoradiotherapy extending beyond 8 months could become a common practice, but not without concerns regarding safety of the subsequent surgical procedures.…”

Section: Discussionmentioning

confidence: 99%

“…The main treatment regimens were S‐1 (oral 5‐fluorouracil prodrug tegafur + oteracil and gimeracil) + radiotherapy; gemcitabine + nab‐paclitaxel; gemcitabine + S‐1; and FOLFIRINOX . On the other hand, patients with UR‐LA were introduced chemotherapy or chemoradiotherapy, especially chemoradiotherapy using gemcitabine + nab‐paclitaxel . Intravenous and intraperitoneal paclitaxel with S‐1 was chosen especially for unresectable disease with peritoneal metastasis (UR‐M) .…”

Section: Methodsmentioning

confidence: 99%

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Effects of duration of initial treatment on postoperative complications in pancreatic cancer

Yamada

Takami

Sonohara

et al. 2019

J Hepato Biliary Pancreat

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Background We analyzed the clinical impact of chemotherapy or chemoradiotherapy as initial treatment (IT), focusing on treatment duration, on morbidity and mortality in patients with resected pancreatic ductal adenocarcinoma. Methods We enrolled 509 consecutive patients, with 417 in the upfront surgery group and 92 in the IT group. The IT group was subdivided into 72 patients treated for <8 months and 20 treated ≥8 months. We compared rates of postoperative Clavien-Dindo grade ≥III complications between the groups. Multivariate logistic regression analysis was used to find independent predictors of complications. Results The upfront surgery and IT groups did not significantly differ in overall postsurgical complications. In contrast, rates of overall complications significantly differed between the <8 months and ≥8 months IT groups, although their background clinical factors did not differ. In multivariate analysis, operative procedure (distal pancreatectomy and distal pancreatectomy with celiac axis resection) (odds ratio [OR] 6.950, P = 0.0416) and IT ≥8 months (OR 4.508, P = 0.0156) were independent predictive factors for postoperative complications. Conclusions Postoperative complications were significantly higher in the ≥8 months IT group, and multivariate analysis demonstrated that operative procedure and ≥8 months IT were independent predictive factors.

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“…Dose-limiting toxicities were defined according to CTCAE version 4.0 12 based on the presence of one or more of the following events: grade 4 leucopenia or neutropenia; grade 3 neutropenia complicated by fever of at least 38 ∘ C; grade 3-4 anaemia, thrombocytopenia or non-haematological toxicities; and more than 2 weeks of drug withdrawal within one cycle. The maximum tolerated dose was determined, and the previous level was set as the recommended dose 13 .…”

Section: Definition Of Dose-limiting Toxicities and Determination Of mentioning

confidence: 99%

Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis

Yamada

Fujii

Yamamoto

et al. 2020

British Journal of Surgery

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Background: Intraperitoneal chemotherapy using paclitaxel is considered an experimental approach for treating peritoneal carcinomatosis. This study aimed to determine the recommended dose, and to evaluate the clinical efficacy and safety, of the combination of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis. Methods: The frequencies of dose-limiting toxicities were evaluated, and the recommended dose was determined in phase I. The primary endpoint of the phase II analysis was overall survival rate at 1 year. Secondary endpoints were antitumour effects, symptom-relieving effects, safety and overall survival. Results: The recommended doses of intravenous gemcitabine, intravenous nab-paclitaxel and intraperitoneal paclitaxel were 800, 75 and 20 mg/m 2 respectively. Among 46 patients enrolled in phase II, the median time to treatment failure was 6⋅0 (range 0-22⋅6) months. The response and disease control rates were 21 of 43 and 41 of 43 respectively. Ascites disappeared in 12 of 30 patients, and cytology became negative in 18 of 46. The median survival time was 14⋅5 months, and the 1-year overall survival rate was 61 per cent. Conversion surgery was performed in eight of 46 patients, and those who underwent resection survived significantly longer than those who were not treated surgically (median survival not reached versus 12⋅4 months). Grade 3-4 haematological toxicities developed in 35 of 46 patients, whereas non-haematological adverse events occurred in seven patients. Conclusion: Adding intraperitoneal paclitaxel had clinical efficacy with acceptable tolerability.

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Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer

Abstract: The RD for weekly administration was 800 mg/m for gemcitabine and 100 mg/m for nab-paclitaxel with a 50.4 Gy radiation. The GnP regimen at this dosage was promising with 6 of 12 patients proceeding to conversion surgery, and should be evaluated further in a phase II trial.

Cited by 22 publications

References 21 publications

Response of patients with locally advanced pancreatic adenocarcinoma to high-intensity focused ultrasound treatment: a single-center, prospective, case series in China

Response of patients with locally advanced pancreatic adenocarcinoma to high-intensity focused ultrasound treatment: a single-center, prospective, case series in China

Effects of duration of initial treatment on postoperative complications in pancreatic cancer

Phase I/II study of adding intraperitoneal paclitaxel in patients with pancreatic cancer and peritoneal metastasis

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