Weekly docetaxel in minimally pretreated cancer patients: A dose-escalation study focused on feasibility and cumulative toxicity of long-term administration

Briasoulis, Evangelos; Karavasilis, Vasilios; Anastasopoulos, D.; Tzamakou, Eleftheria; Fountzilas, George; Rammou, Dimitra; Kostadima, V.; Pavlidis, Nicholas

doi:10.1023/a:1008399712913

Cited by 50 publications

(37 citation statements)

References 16 publications

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“…The better toxicity profile associated with the weekly docetaxel administration has been confirmed in a recently published study. A weekly dose of 50 mg/m 2 (giving a three-week cumulative dose of 150 mg/m 2 ) was the MTD, and even at this level no episodes of grade 4 neutropenia were observed, the DLT also being a prolonged moderate neutropenia causing > 2-week treatment delay in this study [11].…”

Section: Discussionmentioning

confidence: 60%

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Weekly docetaxel plus gemcitabine or vinorelbine in refractory advanced breast cancer patients: A parallel dose-finding study

Frasci¹,

Comella

D’Aiuto

et al. 2000

Annals of Oncology

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SummaryPurpose: The objective of this study was to determine the docetaxel MTD when combined with gemcitabine or vinorelbine in advanced breast cancer patients who had received previous anthracycline-based chemotherapy for advanced disease.Patients and methods: Advanced breast cancer patients aged between 18 and 70 with ECOG PS 0-2 who had not responded to, or had relapsed after, first-line anthracycline-based chemotherapy, were randomized to receive either gemcitabine 1000 mg/m 2 or vinorelbine 25 mg/m 2 in combination with escalating doses of docetaxel (starting from 30 mg/m 2 ), all on days 1 and 8 every three weeks. Escalation was stopped if > 33% of patients treated at a given dose level showed DLTat the first cycle.Results: A total of 34 patients with locally advanced (8) or metastatic disease (26) were treated, for a total of 94 cycles delivered. Nineteen patients received docetaxel in combination with gemcitabine and 15 with vinorelbine. All patients had been pretreated with anthracyclines, and 24 of 34 had also received weekly dose-dense paclitaxel. A docetaxel dose of 40/m 2 proved to be safe when combined on days 1 and 8 with gemcitabine, while a dose of 35 mg/m 2 was tolerated in combination with vinorelbine. Overall, nine episodes of DLT, all of them neutropenia, occurred at the first cycle. Considering all 94 cyles, grades 3 or 4 neutropenia and thrombocytopenia occurred in 15 (44%), and 7 (20%) patients. Non-hematologic toxicity was mild, except for three cases of grade 2 peripheral neuropathy. All patients were assessed for response on an 'intent-to-treat' basis. Overall, five partial responses were recorded (docetaxel + gemcitabine = 3 and docetaxel + vinorelbine = 2), for a 15% (95% CI: 5%-31%) overall response rate. Only 1 of 24 (4%) patients who had received weekly dosedense paclitaxel responded to treatment. Conclusions:The weekly docetaxel administration in combination with either gemcitabine or vinorelbine is a well-tolerated treatment for heavily pretreated advanced breast cancer patients. This approach, although sometimes capable of achieving a major response, does not seem advisable in advanced breast cancer patients refractory to both anthracyclines and paclitaxel.

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Section: Discussionmentioning

confidence: 60%

“…Since it has been recently reported that the weekly schedule could improve the docetaxel therapeutical index [11], we undertook this phase I study with the objective of determining the docetaxel MTD when it is combined with either vinorelbine or gemcitabine in anthrayclinerefractory advanced breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Weekly docetaxel plus gemcitabine or vinorelbine in refractory advanced breast cancer patients: A parallel dose-finding study

Frasci¹,

Comella

D’Aiuto

et al. 2000

Annals of Oncology

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“…Several dosing regimens were evaluated, including: (a) dosing for 2-or 3-week periods followed by a 1-week no-treatment "rest" period [18][19][20], (b) dosing for 4-6 weeks followed by a 2-week rest period [21,22], and (c) continuous weekly dosing without a rest period [23][24][25]. For docetaxel, the infusion duration varied among studies, with the majority using a 1-hour i.v.…”

Section: Preliminary Data With Weekly Taxanes In Solid Tumorsmentioning

confidence: 99%

“…For docetaxel, the infusion duration varied among studies, with the majority using a 1-hour i.v. infusion, which is recommended in current labeling, while two studies used a shorter infusion time (15-30 minutes) [22,23]. For paclitaxel, the infusion duration was 1 hour in all studies.…”

Section: Preliminary Data With Weekly Taxanes In Solid Tumorsmentioning

confidence: 99%

Weekly Administration of Docetaxel and Paclitaxel in Metastatic or Advanced Breast Cancer

2005

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“…This led to the current use of docetaxel and cisplatin combination as one of the most important first-line chemotherapy regimens. Although initial Phase I studies suggested that docetaxel administered on a weekly basis was effective with low toxicity at doses up to 45 mg/m 2,8,9 the combination of docetaxel 75 mg/m 2 and cisplatin 60-80 mg/m 2 administered every 3 weeks is now one of the most commonly used regimens for the first-line treatment of advanced NSCLC.…”

mentioning

confidence: 99%

Randomized phase II trial of two different schedules of docetaxel plus cisplatin as first‐line therapy in advanced nonsmall cell lung cancer

Park

Choi

Kyung

et al. 2007

Cancer

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Livers exposed to warm ischemia (WI) before transplantation are at risk for primary nonfunction (PNF), graft dysfunction, and ischemic biliary strictures, all associated with ischemia/reperfusion injury (IRI). Our multifactorial approach, Leuven drug protocol (LDP), has been shown to reduce these effects and increase recipient survival in WI/IRI‐damaged porcine liver transplantation. The aim was the identification of the molecular mechanisms responsible for the hepatoprotective effects of the LDP. Porcine livers were exposed to 45 minutes of WI, cold‐stored for 4 hours, transplanted, and either modulated (LDP group; n = 3) or not modulated (control group; n = 4). In the LDP group, the donor livers were flushed with streptokinase and epoprostenol before cold perfusion; the recipients received intravenous glycine, a‐1‐acid‐glycoprotein, FR167653 (a mitogen‐activated protein kinase inhibitor), a‐tocopherol, glutathione, and apotransferrin. Liver samples were taken before WI and 1 hour after reperfusion. Gene expression was determined with microarrays and molecular pathways and key regulatory genes were identified. The number of genes changed between baseline and 1 hour after reperfusion was 686 in the LDP group and 325 in the control group. The extra genes in the LDP group belonged predominantly to pathways related to cytokine activity, apoptosis, and cell proliferation. We identified 7 genes that were suppressed in the LDP group. These genes could be linked in part to the administered drugs. New potential drug targets were identified on the basis of genes induced in the control group but unaffected in the LDP group and interactions predicted by the literature. In conclusion, the LDP primarily resulted in the suppression of inflammation‐regulating genes in IRI. Furthermore, the microarray technique helped us to identify additional gene targets. Liver Transpl 18:206–218, 2012. © 2011 AASLD.

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Weekly docetaxel in minimally pretreated cancer patients: A dose-escalation study focused on feasibility and cumulative toxicity of long-term administration

Abstract: Long-term weekly administration of docetaxel is feasible at doses up to 45 mg/m2/week with acceptable toxicity. Further clinical evaluation is justified at this schedule and 40 mg/m2/week of docetaxel is proposed for phase II studies as an active dose with minimal toxicity.

Cited by 50 publications

References 16 publications

Weekly docetaxel plus gemcitabine or vinorelbine in refractory advanced breast cancer patients: A parallel dose-finding study

Weekly docetaxel plus gemcitabine or vinorelbine in refractory advanced breast cancer patients: A parallel dose-finding study

Weekly Administration of Docetaxel and Paclitaxel in Metastatic or Advanced Breast Cancer

Randomized phase II trial of two different schedules of docetaxel plus cisplatin as first‐line therapy in advanced nonsmall cell lung cancer

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