A phase II study

Rougier, Philippe; Adenis, Antoine; Ducreux, Michel; Forni, M; Bonneterre, J.; Dembak, M.; Clouet, P.; Lebecq, A.; Baille, P.; Lefresne-Soulas, F; Blanc, C.; Armand, Jean‐Pierre

doi:10.1016/s0959-8049(00)00072-1

Cited by 183 publications

(10 citation statements)

References 33 publications

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“…Four of 32 eligible patients achieved an objective response (12.5%), and the median overall survival was 4.7 months. In general, single-agent docetaxel activity approximates that of gemcitabine, with response rates ranging from 0% to 20%, median times-to-progression of 1.2-2.1 months, and median survivals of 4-6 months [2][3][4].…”

Section: Discussionmentioning

confidence: 99%

“…Gemcitabine, alone or in combination with erlotinib remains standard of care, but median survival for advanced disease patients approximates only 6 months [1]. Taxanes also have some activity against this tumor; firstline docetaxel offers response rates ranging from 0% to 20%, a median survival of 4-6 months, and median timeto-progression of 1.2-2.1 months [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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Phase II study of calcitriol-enhanced docetaxel in patients with previously untreated metastatic or locally advanced pancreatic cancer

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phase II study of calcitriol-enhanced docetaxel in patients with previously untreated metastatic or locally advanced pancreatic cancer

et al. 2008

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“…As an agent of second-line chemotherapy, docetaxel is one of the most important new and active chemotherapeutic agents developed in recent years, and has potential activity against human solid tumors including pancreatic cancer that are refractory to conventional anticancer agents (Bissery et al, 1995;Kaye, 1995). Recently, several phase II trials of advanced pancreatic cancer have reported high response rates (20%) and relatively long survival after treatment with docetaxel administered at 100 mg/m 2 over a 1-h period (Rougier et al, 2000;Lenzi et al, 2002). However, the use of high-dose docetaxel always induced different levels of toxic reactions, and significant toxicity has precluded the use of docetaxel as a monotherapy for cancer (Cortes and Pazdur, 1995).…”

Section: Introductionmentioning

confidence: 99%

PSK-mediated NF-κB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1

et al. 2003

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Docetaxel, a member of the taxane family, has been shown to induce apoptosis in a variety of cancer cells. However, toxicity at therapeutic doses has precluded the use of docetaxel alone for the management of cancer patients. PSK, a protein-bound polysaccharide, is widely used in Japan as an immunopotentiating biological response modifier for cancer patients. Our previous study showed that PSK induced downregulation of several invasion-related factors, suggesting an interaction of PSK with transcriptional factors. In this study, we showed that PSK dose dependently enhanced apoptosis induced by 1 nm of docetaxel in a human pancreatic cancer cell line NOR-P1. Furthermore, PSK inhibited docetaxel-induced nuclear factor kappa B (NF-jB) activation. Moreover, the expression of cellular inhibitor of apoptosis protein (cIAP-1), which is transcriptionally regulated by NF-jB and functions as an antiapoptotic molecule through interrupting the caspase pathway, was also inhibited by treatment with PSK plus docetaxel. As a result, PSK enhanced the docetaxel-induced caspase-3 activation. In addition, treatment by transfection of NF-jB decoy oligodeoxynucleotides (ODNs), but not scramble ones, inhibited the expression of cIAP-1 in NOR-P1 cells and induced a significant increase in docetaxel-induced apoptosis. Our data indicate that PSK suppresses the docetaxel-induced NF-jB activation pathway. Combination of PSK with a low dose of docetaxel may be a new therapeutic strategy to treat patients with pancreatic cancer.

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“…An objective response rate (RR) of 15% was observed in a phase II study of chemotherapy-naïve patients with advanced PC treated with docetaxel 100 mg/m 2 every 3 weeks. [8] Response rates observed in two other phase II studies of docetaxel utilizing this dose and schedule were 5% and 6%. [9, 10] With lower doses of docetaxel (60 mg/m 2 every three to four weeks), the RR was 0%.…”

Section: Introductionmentioning

confidence: 92%

A Phase II Study of Flavopiridol (Alvocidib) in Combination with Docetaxel in Refractory, Metastatic Pancreatic Cancer

et al. 2009

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Background/Aims: Pancreatic adenocarcinoma (PC) harbors frequent alterations in p16, resulting in cell cycle dysregulation. A phase I study of docetaxel and flavopiridol, a pan-cyclin-dependent kinase inhibitor, demonstrated encouraging clinical activity in PC. This phase II study was designed to further define the efficacy and toxicity of this regimen in patients with previously treated PC. Methods: Patients with gemcitabine-refractory, metastatic PC were treated with docetaxel 35 mg/m² followed by flavopiridol 80 mg/m² on days 1, 8, and 15 of a 28-day cycle. Tumor measurements were performed every two cycles. A Simon two-stage design was used to evaluate the primary endpoint of response. Results: Ten patients were enrolled, and 9 were evaluable for response. No objective responses were observed; however, 3 patients (33%) achieved transient stable disease, with one of these patients achieving a 20% reduction in tumor size. Median survival was 4.2 months, with no patients alive at the time of analysis. Adverse events were significant, with 7 patients (78%) requiring ≥1 dose reduction for transaminitis (11%), grade 4 neutropenia (33%), grade 3 fatigue (44%), and grade 3 diarrhea (22%). Conclusions: The combination of flavopiridol and docetaxel has minimal activity and significant toxicity in this patient population. These results reflect the challenges of treating patients with PC in a second-line setting where the risk/benefit equation is tightly balanced.

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A phase II study

Cited by 183 publications

References 33 publications

Phase II study of calcitriol-enhanced docetaxel in patients with previously untreated metastatic or locally advanced pancreatic cancer

Phase II study of calcitriol-enhanced docetaxel in patients with previously untreated metastatic or locally advanced pancreatic cancer

PSK-mediated NF-κB inhibition augments docetaxel-induced apoptosis in human pancreatic cancer cells NOR-P1

A Phase II Study of Flavopiridol (Alvocidib) in Combination with Docetaxel in Refractory, Metastatic Pancreatic Cancer

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