Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age = grade 3 was observed in the standard arm of the D4 study compared to the weekly schedule (per-patient analysis: 61.9% q3w vs. 65.1% q1w; p > 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy. Copyright (C) 2011 S. Karger AG, Base

Abenhardt, Wolfgang

Artmann, Almut

de Rivera, Isolde Groell

Harbeck, Nadia

Heinemann, Volker

Kaiser, Ursula Vehling

Kiechle, Marion

Meerpohl, Hans-Gerd

Rauthe, Gerhard

Sommer, Harald

Stemmler, Hans-Joachim

English

Purpose: Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to randomly compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application. Methods: Patients previously untreated with chemotherapy for metastatic disease were recruited. Patients aged >60 years or with a Karnofsky Perfomance Status (KPS) of 60-80% were eligible for the D2 study. Patients were randomized to receive docetaxel either on a 3-weekly {[}75 mg/m(2) every 3 weeks (q3w)] or on a weekly (30 mg/m(2) on days 1, 8, and 15; q4w) schedule. Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. Results: Since statistical significance for the primary endpoint (toxicity) was achieved in the interim analysis, the study was closed according to the study protocol (102 of 162 patients). Compared to the standard arm, leukopenia >= grade 3 was a rare event in the weekly arm of the D2 study (per-patient analysis: 4.2% q1w vs. 51.9% q3w; p < 0.0001). No difference was observed between the 2 schedules regarding the occurrence of anemia or thrombocytopenia. With regard to non-hematological toxicity, there was a higher incidence of skin/nail and hepatological toxicity with the weekly schedule, whereas neurotoxicity was observed more often in the standard arm. The rate of omitted doses was significantly increased in the weekly arm (8.6% q1w vs. 0% q3w). The overall response rate was 22.9% in the weekly arm compared to 42.6% in the standard arm (p = 0.039). Time to progression was 5.4 (q1w) versus 6.3 (q3w) months (p = 0.91), and overall survival was 22.7 (q1w) versus 15.8 (q3w) months (p = 0.24). Conclusion: The present data support the feasibility of both weekly and 3-weekly application of docetaxel. As expected, severe leukopenia seems avoidable in weekly scheduled single-agent docetaxel and may serve as an important treatment option, particularly in elderly patients and patients with a reduced performance status. Copyright (C) 2011 S. Karger AG, Base

Universität München: Elektronischen Publikationen

Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel (D2) for First-Line Treatment of Metastatic Breast Cancer

&lt;i&gt;Purpose:&lt;/i&gt; Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application in combination with doxorubicin. &lt;i&gt;Methods:&lt;/i&gt; Patients previously untreated with chemotherapy for metastatic disease were recruited. Inclusion criteria were age &lt;65 years or a Karnofsky Performance Status of 70–100%. All patients in the D4 study received doxorubicin (50 mg/m&lt;sup&gt;2&lt;/sup&gt;) on the first day of treatment in addition to docetaxel given either at a 3-weekly dose of 75 mg/m&lt;sup&gt;2&lt;/sup&gt; every 3 weeks (q3w) or at a weekly dose of 35 mg/m&lt;sup&gt;2&lt;/sup&gt; (days 1, 8, and 15; q4w). Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. &lt;i&gt;Results:&lt;/i&gt; Since interim analysis showed failure to reach a significant difference for the primary endpoint (hematotoxicity, i.e. leukopenia), the study was closed according to the study protocol (85 of 242 patients). A lower-than-expected rate of leukopenia ≧grade 3 was observed in the standard arm of the D4 study compared to the weekly schedule (per-patient analysis: 61.9% q3w vs. 65.1% q1w; p &gt; 0.05). Grade 3 and grade 4 fever, diarrhea, and infections occurred more frequently in the standard arm, whereas neurotoxicity and skin/nail disorders were observed more frequently in the weekly arm. Except for fever, none of these differences reached a level of significance. Dose delays, dose reductions, and the rate of omitted doses were increased in the weekly arm. The overall response rate was 44.2% in the weekly arm compared to 52.4% in the standard arm (p = 0.52). Time to progression was 6.2 (q1w) versus 10.3 (q3w) months (p = 0.36), and overall survival was 20.5 (q1w) versus 28.7 (q3w) months (p = 0.98). &lt;i&gt;Conclusion:&lt;/i&gt; The present data support the feasibility of both weekly and 3-weekly application of docetaxel in combination with doxorubicin. Nevertheless, given that leukopenia was similar in both arms and the efficacy parameters were at least numerically inferior with the weekly schedule, standard 3-weekly application seems to be preferable for patients requiring combination chemotherapy.</jats:p

Hans-Joachim Stemmler

Nadia Harbeck

Isolde Gröll de Rivera

Ursula Vehling Kaiser

Gerhard Rauthe

Wolfgang Abenhardt

Almut Artmann

Harald Sommer

Hans-Gerd Meerpohl

Marion Kiechle

Volker Heinemann

Crossref

Oncology

Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel plus Doxorubicin (D4) for First-Line Treatment of Metastatic Breast Cancer

Open Access LMU

Assadourian S: Docetaxel versus 5-fluorouracil plus vinorelbine in metastatic breast cancer after anthracycline therapy failure.

DR: The Analysis of Binary Data.

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EP: Docetaxel administered on a weekly basis for metastatic breast cancer.

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Goldhirsch A: Epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer: a multicentric phase I–II study. Ann Oncol

Greco FA: Weekly administration of docetaxel (Taxotere): summary of clinical data. Semin Oncol

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Weekly docetaxe l ( T a x o t e r e ) i n p a t i e n t s w i t h m e t a s t a t i c breast cancer. Ann Oncol

&lt;i&gt;Purpose:&lt;/i&gt; Previous phase II studies have indicated a greatly reduced hematotoxicity of docetaxel-based regimens administered on weekly schedules. The present trial was initiated to randomly compare the toxicity and efficacy of weekly docetaxel versus its standard 3-weekly application. &lt;i&gt;Methods:&lt;/i&gt; Patients previously untreated with chemotherapy for metastatic disease were recruited. Patients aged &gt;60 years or with a Karnofsky Perfomance Status (KPS) of 60–80% were eligible for the D2 study. Patients were randomized to receive docetaxel either on a 3-weekly [75 mg/m&lt;sup&gt;2&lt;/sup&gt; every 3 weeks (q3w)] or on a weekly (30 mg/m&lt;sup&gt;2&lt;/sup&gt; on days 1, 8, and 15; q4w) schedule. Treatment was continued until a maximum of 8 cycles, unacceptable toxicity, or disease progression. All patients received standard corticosteroid prophylaxis. &lt;i&gt;Results:&lt;/i&gt; Since statistical significance for the primary endpoint (toxicity) was achieved in the interim analysis, the study was closed according to the study protocol (102 of 162 patients). Compared to the standard arm, leukopenia ≧grade 3 was a rare event in the weekly arm of the D2 study (per-patient analysis: 4.2% q1w vs. 51.9% q3w; p &lt; 0.0001). No difference was observed between the 2 schedules regarding the occurrence of anemia or thrombocytopenia. With regard to nonhematological toxicity, there was a higher incidence of skin/nail and hepatological toxicity with the weekly schedule, whereas neurotoxicity was observed more often in the standard arm. The rate of omitted doses was significantly increased in the weekly arm (8.6% q1w vs. 0% q3w). The overall response rate was 22.9% in the weekly arm compared to 42.6% in the standard arm (p = 0.039). Time to progression was 5.4 (q1w) versus 6.3 (q3w) months (p = 0.91), and overall survival was 22.7 (q1w) versus 15.8 (q3w) months (p = 0.24). &lt;i&gt;Conclusion:&lt;/i&gt; The present data support the feasibility of both weekly and 3-weekly application of docetaxel. As expected, severe leukopenia seems avoidable in weekly scheduled single-agent docetaxel and may serve as an important treatment option, particularly in elderly patients and patients with a reduced performance status.</jats:p

https://epub.ub.uni-muenchen.de/16503/1/10_1159_000320625.pdf

Prospective Multicenter Randomized Phase III Study of Weekly versus Standard Docetaxel plus Doxorubicin (D4) for First-Line Treatment of Metastatic Breast Cancer

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Universität München: Elektronischen Publikationen

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Universität München: Elektronischen Publikationen

Open Access LMU

Open Access LMU

Crossref