A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma: cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen)

Reni, Michele; Cereda, Stefano; Rognone, Alessia; Belli, Carmen; Ghidini, Michele; Longoni, Simonetta; Fugazza, Clara; Rezzonico, Sara; Passoni, P.; Slim, N.; Balzano, Gianpaolo; Nicoletti, Roberto; Cappio, Stefano; Doglioni, Claudio; Villa, Eugenio

doi:10.1007/s00280-011-1680-2

Cited by 58 publications

(44 citation statements)

References 34 publications

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“…An alternate every-28-day cycle schedule of docetaxel, gemcitabine, and capecitabine was reported by Xenidis and colleagues that achieved a response rate of 40% and median survival of 9 months (47). Reni and colleagues evaluated an intensive four-drug regimen by adding cisplatin to docetaxel, gemcitabine, and capecitabine in first-line metastatic patients and achieved a response rate of 57% but a disappointing median survival of 5.8 months (48). The efficacy and toxicity profiles of GTX seemed comparable with those reported in the phase I/II trial of nab-paclitaxel-gemcitabine by von Hoff and colleagues (Table 2; ref.…”

Section: Docetaxel-in the Context Of "Gtx"supporting

confidence: 65%

The Winning Formulation: The Development of Paclitaxel in Pancreatic Cancer

Wee

Hidalgo

2013

Clinical Cancer Research

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Paclitaxel has wide application in anticancer therapy but was never considered an efficacious agent in pancreatic cancer. A review of the experience with the Cremaphor formulation hinted at paclitaxel's activity in pancreatic cancer, but the early development was hampered by significant toxicities such as neutropenia and infection at clinically tolerable doses. However, such efficacy was confirmed in the recently completed phase III Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), in which the addition of nabpaclitaxel to gemcitabine significantly improved the survival of patients with metastatic pancreatic cancer. Several other Cremaphor-free formulations of paclitaxel had also been evaluated in pancreatic cancer, and the reasons for the success of the albumin nanoparticulate are examined here. In the era of biologic and molecularly targeted agents, the success of nab-paclitaxel in recalcitrant pancreatic cancer is a timely reminder of the importance and relevance of pharmacology and novel drug delivery technology in the development of anticancer drugs.

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Section: Docetaxel-in the Context Of "Gtx"supporting

confidence: 65%

The Winning Formulation: The Development of Paclitaxel in Pancreatic Cancer

Wee

Hidalgo

2013

Clinical Cancer Research

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“…This trial was designed as a single-centre, prospective, open-label, randomized, phase II study in which patients with pathology-confirmed diagnosis of metastatic pancreatic adenocarcinoma, were randomized to receive metformin (2 g/die; arm A) or not (arm B) in association with our standard four-drug chemotherapy regimen including cisplatin, epirubicin, capecitabine, gemcitabine (PEXG) (41). The primary outcome measure was the progression-free survival at 6 months from treatment start (PFS-6).…”

Section: Methodsmentioning

confidence: 99%

“…Patients in arm A also received metformin 2 g/ day. Guidelines for dose-reduction and treatment delay have been previously reported (41). Treatment was administered for 6 months with a maximum of 6 cycles or interrupted in the case of recurrence or progression, unacceptable toxicity, medical decision, or patient's refusal.…”

Section: Treatment Schedulementioning

confidence: 99%

(Ir)relevance of Metformin Treatment in Patients with Metastatic Pancreatic Cancer: An Open-Label, Randomized Phase II Trial

Reni

Dugnani

Cereda

et al. 2016

Clinical Cancer Research

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155

127

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Purpose: We aimed to assess the safety and efficacy of metformin for treating patients with metastatic pancreatic cancer and to identify endocrine and metabolic phenotypic features or tumor molecular markers associated with sensitivity to metformin antineoplastic action.Experimental Design:We designed an open-label, randomized, phase II trial to assess the efficacy of adding metformin to a standard systemic therapy with cisplatin, epirubicin, capecitabine, and gemcitabine (PEXG) in patients with metastatic pancreatic cancer. Patients ages 18 years or older with metastatic pancreatic cancer were randomly assigned (1:1) to receive PEXG every 4 weeks in combination or not with 2 g oral metformin daily. The primary endpoint was 6-months progression-free survival (PFS-6) in the intention-to-treat population.Results: Between August 2010 and January 2014, we randomly assigned 60 patients to receive PEXG with (n ¼ 31) or without metformin (n ¼ 29). At the preplanned interim analysis, the study was ended for futility. PFS-6 was 52% [95% confidence interval (CI), 33-69] in the control group and 42% (95% CI, 24-59) in the metformin group (P ¼ 0.61). Furthermore, there was no difference in disease-free survival and overall survival between groups. Despite endocrine metabolic modifications induced by metformin, there was no correlation with the outcome. Single-nucleotide polymorphism rs11212617 predicted glycemic response, but not tumor response to metformin. Gene expression on tumor tissue did not predict tumor response to metformin.Conclusions: Addition of metformin at the dose commonly used in diabetes did not improve outcome in patients with metastatic pancreatic cancer treated with standard systemic therapy.

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“…Furthermore, some studies have reported a survival benefit when adding docetaxel to the cisplatin-based regimen in patients with advanced pancreatic adenocarcinoma or non-small cell lung cancer (mainly adenocarcinoma). 8,9 TPF with radiation achieved a local complete response in case 2 (adenocarcinoma), but the lung metastasis remained viable. Concurrent radiotherapy might have synergistic antitumor activity in adenocarcinoma, as is seen in SCC.…”

Section: Discussionmentioning

confidence: 97%

Docetaxel, cisplatin and 5‐fluorouracil chemotherapy with concurrent radiation for unresectable advanced urethral carcinoma

et al. 2013

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Abbreviations & AcronymsAbstract: The present case report describes two cases of unresectable advanced primary urethral carcinoma. Case 1 was a 61-year-old man with squamous cell carcinoma of the urethra that directly invaded into the perineal skin. Case 2 was a 64-year-old woman with adenocarcinoma, and solitary lung and lymph node metastases. Both patients received docetaxel/cisplatin/5-fluorouracil chemotherapy with concurrent radiation. The docetaxel/cisplatin/5-fluorouracil chemotherapy regimen consisted of docetaxel (75 mg/m 2 ) on day 2, cisplatin (100 mg/m 2 ) on day 2 and 5-fluorouracil (1000 mg/m 2 ) on days 1 to 5 and was repeated every 4 weeks. Complete response was achieved after two cycles of chemotherapy combined with radiation in case 1. In case 2, complete response was achieved locally after six cycles of chemotherapy combined with radiation, but the solitary lung lesion remained viable. We experienced two cases with advanced urethral carcinoma for whom docetaxel/cisplatin/5-fluorouracil chemotherapy chemotherapy with radiation was effective.

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A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma: cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen)

Abstract: The inclusion of D instead of E yielded more objective response and less G3-4 neutropenia but did not improve PFS and OS. The present trial confirms the relevant impact on outcome of advanced PA of 4-drug regimens.

Cited by 58 publications

References 34 publications

The Winning Formulation: The Development of Paclitaxel in Pancreatic Cancer

The Winning Formulation: The Development of Paclitaxel in Pancreatic Cancer

(Ir)relevance of Metformin Treatment in Patients with Metastatic Pancreatic Cancer: An Open-Label, Randomized Phase II Trial

Docetaxel, cisplatin and 5‐fluorouracil chemotherapy with concurrent radiation for unresectable advanced urethral carcinoma

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