Prospective Randomized Trial of Docetaxel Versus Doxorubicin in Patients With Metastatic Breast Cancer

Chan, Stephen Y.; Friedrichs, Kay; Noel, D.; Pintér, Tamás; Belle, Simon Van; Vorobiof, Daniel; Duarte, Ricardo Jordão; Gil, Miguel Gil; Bodrogi, I.; Murray, Elizabeth; Yelle, Louise; Minckwitz, Gϋnter von; Korec, S; Simmonds, Peter; Buzzi, Franco; Mancha, Rosario González; Richardson, Gary; Walpole, Euan; Ronzoni, Monica; Murawsky, Michael; Alakl, May; Riva, A.; Crown, John

doi:10.1200/jco.1999.17.8.2341

Cited by 590 publications

(279 citation statements)

References 26 publications

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“…Combining the results of this study with the two published reports DaunoXome has shown objective responses in eight out of 35 (23%) evaluable patients (Anonymous, 1996;Darskaia et al, 1999). The response rate for this relatively non-toxic anthracycline based therapy must be taken in context with those reported for single-agent doxorubicin which vary from 30 -34% in recent randomised phase III studies (Henderson et al, 1989;Sledge et al, 1997;Chan et al, 1999;Norris et al, 2000). The overall time to tumour progression of 5 months (8.5 months in those patients treated at 120 and 150 mg m 2 ) and median survival of 13.75 months are in keeping with the results reported for large randomised studies of doxorubicin when used alone or as part of a combination regimen in the treatment of symptomatic relapsed breast cancer (Norris et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

et al. 2002

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The aims of this phase I study were to establish the maximum tolerated dose, safety profile and activity of liposomal daunorubicin, DaunoXome (NeXstar Pharmaceuticals), in the treatment of metastatic breast cancer. DaunoXome was administered intravenously over 2 h in 21 day cycles and doses were increased from 80 to 100, 120 and 150 mg m 2 . Sixteen patients were enrolled. A total of 70 cycles of DaunoXome were administered. The maximum tolerated dose was 120 mg m 2 , the dose-limiting toxicity being prolonged grade 4 neutropenia or neutropenic pyrexia necessitating dose reductions at 120 and 150 mg m 2 . Asymptomatic cardiotoxicity was observed in three patients: grade 1 in one treated with a cumulative dose of 800 mg m 2 and grade 2 in two, one who received a cumulative dose of 960 mg m 2 and the other a cumulative dose of 600 mg m 2 with a previous neoadjuvant doxorubicin chemotherapy of 300 mg m 2 . Tumour response was evaluable in 15 patients, of whom two had objective responses, six had stable disease and seven had progressive disease. In conclusion, DaunoXome is associated with mild, manageable toxicities and has anti-tumour activity in metastatic breast cancer. The findings support further phase II evaluation of DaunoXome alone and in combination with other standard nonanthracycline cytotoxic or novel targeted agents. Although the dose-limiting toxicity for DaunoXome was febrile neutropenia at 120 mg m 2 , we would recommend this dose for further evaluation, as the febrile neutropenia occurred after four or more cycles in three of the four episodes seen, was short lived and uncomplicated.

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Section: Discussionmentioning

confidence: 99%

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

et al. 2002

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“…As a single agent, docetaxel has shown marked clinical activity in the treatment of anthracycline-resistant and chemotherapy-naïve (for metastatic disease) breast cancer, achieving response rates of 34 and 50 -72%, respectively (Ravdin et al, 1995;Valero et al, 1995;Marty et al, 1997;Valero, 1997). In a randomised phase III trial in first-line metastatic breast cancer docetaxel (100 mg m À2 ) exhibited superior efficacy and tolerability compared with doxorubicin (at the optimal dose of 75 mg m À2 ) (Chan et al, 1999). The role of docetaxel (both as a single agent and in combination) in early or locally advanced breast cancer is currently being investigated (Gradishar, 1997;Mamounas, 1998;Costa et al, 1999).…”

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confidence: 99%

Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate

et al. 2003

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Docetaxel (Taxotere s ), alone or in combination with other anticancer agents, has proven efficacy in the first-and second-line treatment of metastatic breast cancer. This phase II study investigated the efficacy and tolerability of docetaxel as neoadjuvant chemotherapy in women with stage II -III primary operable breast cancer. Patients (n ¼ 88) were treated with six cycles of docetaxel at 100 mg m À2 every 21 days, followed by definitive surgery and radiotherapy. After six cycles of docetaxel, the overall clinical response rate was 68.4% (CI 95%: 58.1 -78.7%), including 19.0% complete remissions. Breast conservation was achieved in 72.4% of patients. A high pathological complete response (pCR) rate in breast was confirmed in 15 patients (19.8% (CI 95%: 10.8 -28.8%)) on Chevallier's classification restricted to breast and in 27 patients (35.5% (CI 95%: 24.7 -46.3%)) on Sataloff's classification. After a median follow-up of 30.8 months, 19 recurrences were documented with a median time to first recurrence of 17.3 months. Patients with stage III tumours had more recurrences than patients with stage II tumours (P ¼ 0.02). The principal toxicity of docetaxel is myelosuppression and 70.5% of patients developed grade III or IV neutropenia with 13.6% developing neutropenic sepsis. There was no case of severe cardiac toxicity, thrombocytopenia or any other serious adverse events. In conclusion, neoadjuvant docetaxel induces a high pCR and breast-conservation rate. Docetaxel monotherapy is a highly effective regimen that merits formal comparison with currently used combination regimens in a randomised phase III study.

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“…A recent large randomised trial demonstrated improved survival with docetaxel compared with combination therapy with mitomycin C plus vinblastine in patients with MBC who had progressed despite prior anthracycline-containing chemotherapy (Nabholtz et al, 1999). In another multicentre, randomised phase III trial a higher response rate was observed with docetaxel (47.8%) compared with doxorubicin (33.3%) in patients with MBC who had received prior alkylating agent-containing chemotherapy (Chan et al, 1999).…”

Section: Docetaxel Plus Fec In Metastatic Breast Cancer M Spielmann Ementioning

confidence: 94%

“…The anthracyclines have long been considered to be the most active agents in MBC, with reported response rates of about 50% for monotherapy (Findlay and Walker-Dilks, 1998;Ormrod et al, 1999). Of the newer agents now available, docetaxel (Taxotere), a semi-synthetic taxoid, has shown the most promising activity of all the compounds used so far in MBC, even in anthracycline-resistant tumours (Van Oosterom, 1995;Bonneterre et al, 1999;Chan et al, 1999;Nabholtz et al, 1999;Sjöström et al, 1999). Several phase III trials have now established docetaxel as the most active single agent in MBC (Chan et al, 1999;Nabholtz et al, 1999).…”

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confidence: 99%

Sequential or alternating administration of docetaxel (Taxotere®) combined with FEC in metastatic breast cancer: a randomised phase II trial

et al. 2002

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The aim of this study, using a Fleming single-stage design, was to explore the efficacy and safety of Taxotere 1 100 mg m 72 docetaxel and FEC 75 cyclophosphamide 500 mg m 72 , fluorouracil 500 mg m 72 and epirubicin 75 mg m 72 , in alternating and sequential schedules for the first-line treatment of metastatic breast cancer. One hundred and thirty-six women were randomly allocated, to one of three treatment regimens: DTX 100 plus FEC 75, alternated for eight courses (ALT); four courses of DTX 100 followed by four courses of FEC 75 (SEQ T); or four courses of FEC 75 followed by four courses of DTX 100 (SEQ F). One hundred and thirty-one women were evaluable for tumour response. Although the treatment outcome was equivalent in the two sequential arms and the alternating regimen (P=0.110, not significant), the response rate was less encouraging in the SEQ F arm (52.3%) than in the other two arms (71.1% for ALT and 70.5% for SEQ T), in which docetaxel was administered first. Time to progression was similar in the ALT, SEQ T and SEQ F arms (9.5, 9.3 and 10.4 months respectively). Grade 3 -4 neutropenia was observed in nearly all patients; febrile neutropenia occurred in 9% (ALT), 16% (SEQ T) and 2% (SEQ F) of patients. Few patients (49%) developed grade 3 -4 non-haematological toxicities. Relative dose intensity was 97 -99% for all regimens. All treatment regimens were active and well tolerated.

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Prospective Randomized Trial of Docetaxel Versus Doxorubicin in Patients With Metastatic Breast Cancer

Cited by 590 publications

References 26 publications

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate

Sequential or alternating administration of docetaxel (Taxotere®) combined with FEC in metastatic breast cancer: a randomised phase II trial

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