Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group

Sjöström, Johanna; Blomqvist, Carl; Mouridsen, Henning T.; Płużańska, A; Ottosson-Lönn, S; Bengtsson, Nils‐Olof; Østenstad, Bjørn; Mjaaland, Ingvil; Palm-Sjövall, M; Wist, Erik; Valvere, Vahur; Anderson, Harald; Bergh, Jonas

doi:10.1016/s0959-8049(99)00122-7

Cited by 249 publications

(138 citation statements)

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“…The overall response rate (CR þ PR) was 47% after first-line anthracycline therapy, 46% in the docetaxel arm and 26% in the MF arm, respectively. In the parent study (n ¼ 283), the corresponding response rates for docetaxel and MF treatment were 42 and 21% (Sjöström et al, 1999). Association of the overall response rate (complete or partial response) with the investigated tumour proliferation markers is shown in Table 4.…”

Section: Resultsmentioning

confidence: 99%

“…The study is based on a phase III multicentre trial, where 140 patients were randomly allocated to receive intravenous methotrexate and 5-fluorouracil, and 143 to receive intravenous docetaxel until disease progression as second-line therapy for metastatic breast cancer between December 1994 and October 1997 (Sjöström et al, 1999). The patients were required to have histologically proven primary breast cancer that had progressed during or after the first-line anthracycline-containing treatment for metastatic disease, or that had relapsed within 12 months after discontinuation of adjuvant anthracycline-containing regimen.…”

Section: Patientsmentioning

confidence: 99%

“…To our knowledge, there are no studies of cyclin A as a predictive marker for chemotherapy response in metastatic breast cancer. The purpose of the present study is to evaluate cyclin A as a marker for tumour aggressiveness and chemotherapy response in patients with advanced breast cancer treated in a randomised trial (Sjöström et al, 1999).…”

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Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer

et al. 2005

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We wanted to study cyclin A as a marker for prognosis and chemotherapy response. A total of 283 women with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel to sequential methotrexate-fluorouracil (MF) in advanced breast cancer after anthracycline failure. Paraffin-embedded blocks of the primary tumour were available for 96 patients (34%). The proportion of cells expressing cyclin A was determined by immunohistochemistry using a mouse monoclonal antibody to human cyclin A. Response evaluation was performed according to WHO recommendations. The median cyclin A positivity of tumour cells was 14.5% (range 1.2 -45.0). Cyclin A correlated statistically significantly to all other tested proliferation markers (mitotic count, histological grade and Ki-67). A high cyclin A correlated significantly to a shorter time to first relapse, risk ratio (RR) 1.94 (95% CI 1.24 -3.03) and survival from diagnosis, RR 2.49 (95% CI 1.45 -4.29), cutoff point for high/low proliferation group 10.5%. Cyclin A did not correlate to chemotherapy response or survival after anthracycline, docetaxel or MF therapy. Of all tumour biological factors tested (mitotic count, histological grade and Ki-67), cyclin A seemed to have the strongest prognostic value. Cyclin A is a good marker for tumour proliferation and prognosis in breast cancer. In the present study, cyclin A did not predict chemotherapy response.

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Section: Resultsmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

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Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer

et al. 2005

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“…has demonstrated a broad spectrum of activity against a variety of advanced solid tumours, and breast cancer represents the first in which docetaxel has been successfully tested (Salminen et al, 1999). In particular, for patients with prior anthracycline-based therapy, taxanes represent the treatment of choice in the salvage setting, since previously applied agents have demonstrated inferior activity, taxanes have exhibited a relative lack of cross-resistance with anthracyclines, and have so far demonstrated fair tolerability in pretreated patients.Three second-line phase III studies in anthracycline-refractory patients evaluated single-agent docetaxel vs salvage regimens thought to be active in this setting, namely mitomycin-C+vinblas-tine (Nabholtz et al, 1999), methotrexate -5-fluorouracil (5-FU) (Sjostrom et al, 1999), and infusional 5-FU+vinorelbine (Monnier et al, 1998). Two of the above studies (Nabholtz et al, 1999;Sjostrom et al, 1999) demonstrated an advantage in favour of docetaxel with respect to response rate (RR) and time to progression (TTP), while only the study of Nabholtz et al (1999) so far reported a significant 3-month prolongation in median overall survival (OS), while, in contrast, the third study by Monnier et al (1998) did not report any advantage of docetaxel vs infusional 5-FU+vinorelbine.…”

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confidence: 99%

Phase I–II study of docetaxel and ifosfamide combination in patients with anthracycline pretreated advanced breast cancer

Kosmas

Tsavaris²,

Malamos

et al. 2003

Br J Cancer

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Given the established individual activity of docetaxel and ifosfamide in anthracycline pretreated advanced breast cancer, the present phase I -II study aimed to define the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and activity of the docetaxel -ifosfamide combination in this setting. Cohorts of three to six patients with histologically confirmed metastatic breast cancer after prior anthracycline-based chemotherapy were treated at successive dose levels (DLs) with escalated doses of docetaxel 70 -100 mg m À2 over 1 h on day 1 followed by ifosfamide 5 -6 g m À2 divided over days 1 and 2 (2.5 -3.0 g m À2 day À1 over 1 h), and recycled every 21 days. G-CSF was added once dose-limiting neutropenia was encountered at a certain DL and planned to be incorporated prophylactically in subsequent higher DLs. In total, 56 patients with a median age of 54.5 (range, 32 -72) years and performance status (WHO) of 1 (range, 0 -2) were treated at five DLs as follows: 21 in phase I DLs (DL1: 3, DL2: 6, DL3: 3, DL4: 6, and DL5: 3) and the remaining 35 were treated at DL4 (total of 41 patients at DL4), which was defined as the level for phase II testing. All patients were assessable for toxicity and 53 for response. Dose-limiting toxicity (with the addition of G-CSF after DL2) was reached at DL5 with two out of three initial patients developing febrile neutropenia (FN). Clinical response rates, on an intention-to-treat basis, in phase II were: 53.6% (95% CI, 38.3 -68.9%); three complete remissions, 19 partial remissions, seven stable disease, and 12 progressive disease. The median response duration was 7 months (3 -24 months), median time to progression 6.5 month (0.1 -26 month), and median overall survival 13 months (0.1 -33 months). Grade 3/4 toxicities included time to progression neutropenia in 78% of patients -with 63% developing grade 4 neutropenia (p7 days) and in 12% of these FN, while no grade 3/4 thrombocytopenia was observed. Other toxicities included peripheral neuropathy grade 2 only in 12%, grade 1/2 reversible CNS toxicity in 17%, no renal toxicity, grade 2 myalgias in 10%, grade 3 diarrhoea in 10%, skin/nail toxicity in 17%, and grade 2 fluid retention in 2% of patients. One patient in the study treated at phase II died as a result of acute liver failure after the first cycle. In conclusion, the present phase I -II study determined the feasibility of the docetaxel -ifosfamide combination, defined the MTD and demonstrated the encouraging activity of the regimen in phase II, thus warranting further randomised phase III comparisons to singleagent docetaxel or combinations of the latter with other active agents. ) has demonstrated a broad spectrum of activity against a variety of advanced solid tumours, and breast cancer represents the first in which docetaxel has been successfully tested (Salminen et al, 1999). In particular, for patients with prior anthracycline-based therapy, taxanes represent the treatment of choice in the salvage setting, since previously applied agents have demonstrated infe...

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“…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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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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Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group

Cited by 249 publications

References 6 publications

Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer

Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer

Phase I–II study of docetaxel and ifosfamide combination in patients with anthracycline pretreated advanced breast cancer

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

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