Weekly paclitaxel-cisplatin administration with G-CSF support in advanced breast cancer. A phase II study

Giuseppe Frasci, Pasquale Comella, Giuseppe D'Aiuto, Alfredo Budillon, Deborah Barbarulo, Renato Thomas, Immacolata Capasso, Rossana Casaretti, Antonio Daponte, Francesco Caponigro, Adriano Gravina, Luigi Maiorino, Giacomo Caratení, Alfonso Gentile, Giuseppe Comella

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Purpose: In a previous phase I study we found the MTDs of paclitaxel and cisplatin when given together weekly, with or without G-CSF support, in patients with advanced solid tumors. The present study was conducted to define the toxicity and efficacy of this regimen, when used with G-CSF support, in chemotherapy-naive or pretreated patients with advanced breast cancer, and to compare the antiproliferative activity of paclitaxel-cisplatin and paclitaxel-doxorubicin combinations on two human breast cancer cell lines. Methods: Patients with metastatic breast cancer received weekly paclitaxel (as a 3-hour IV infusion) at the dose of 85 mg/m2 (75 mg/m2 in pretreated women) followed by cisplatin (40 mg/m2) for a minimum of 6 weeks. An additional 6 weekly cycles were delivered in patients showing absence of documented disease progression after the first 6 weeks. After the 12th cycle only patients who had shown a substantial tumor shrinkage received 6 further cycles. G-CSF 5 μg/kg was also given, SC on days 3 to 5 of each week, for the whole duration of chemotherapy. The combination of paclitaxel with cisplatin or doxorubicin was also tested in vitro on two breast cancer cell lines (MCF-7 and MDAMB-231). Results: Forty-three women with metastatic breast cancer entered this trial between June 1995 and January 1997. Twenty-seven patients were previously untreated for their metastatic disease (but 23 had previously received adjuvant chemotherapy). The dominant site of disease involvement was visceral in 23, bone in 13, and soft tissues in 7 patients. Seven complete and 15 partial responses were observed in unpretreated patients, while no complete and 6 partial responses were achieved in the pretreated population. The overall response rate, assessed on an 'intent to treat' basis, was 81% (26% CRs) in patients unpretreated for metastatic disease and 37% in those who had received one or more previous chemotherapy regimens. Eighteen responder patients had previously received anthracyclines either as adjuvant chemotherapy (12) or in the treatment of metastatic disease (6). At a median potential follow-up of 12 (range, 3-21) months, 14/27 unpretreated and 12/16 pretreated patients had shown disease progression. The median time to treatment failure was 13 and 7 months, respectively, in the 2 subgroups. The 1-year survival probability was 95% in unpretreated patients. The treatment showed a moderate toxicity in both subgroups of patients. Both hematological toxicity and peripheral neuropathy occurred more frequently in pretreated patients. Treatment-related deaths did not occur, and severe myelosuppression was observed only in pretreated patients with massive liver involvement. Delays in chemotherapy administration were very uncommon, especially during the first 6 treatment cycles, and the average actually delivered dose intensity exceeded 90% in unpretreated patients. The in vitro data on MCF-7 and MDA-MB-231 human breast cancer cell lines showed that exposure to the combination of cisplatin and paclitaxel produced a tumor cell killing similar to that achievable with equivalent concentrations of doxorubicin and paclitaxel. Conclusions: Weekly paclitaxel and cisplatin with G-CSF support is an active and particularly well tolerated treatment for patients with either unpretreated or pretreated metastatic breast cancer. This approach seems quite effective also in patients relapsing after anthracycline-based adjuvant chemotherapy. In view of the negligible hematological toxicity associated with this regimen, further clinical trials testing the addition of non cross-resistant drugs to this combination should be performed.

Original languageEnglish
Pages (from-to)13-26
Number of pages14
JournalBreast Cancer Research and Treatment
Volume49
Issue number1
DOIs
Publication statusPublished - 1998

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Granulocyte Colony-Stimulating Factor
Breast Neoplasms
Adjuvant Chemotherapy
Paclitaxel
Doxorubicin
TP protocol
Drug Therapy
Anthracyclines
Cell Line
Disease Progression
Therapeutics
Neoplasms
Peripheral Nervous System Diseases
Drug Combinations
Treatment Failure

Keywords

  • Advanced breast cancer
  • Chemotherapy
  • Cisplatin
  • Paclitaxel
  • Weekly schedule

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Weekly paclitaxel-cisplatin administration with G-CSF support in advanced breast cancer. A phase II study. / Frasci, Giuseppe; Comella, Pasquale; D'Aiuto, Giuseppe; Budillon, Alfredo; Barbarulo, Deborah; Thomas, Renato; Capasso, Immacolata; Casaretti, Rossana; Daponte, Antonio; Caponigro, Francesco; Gravina, Adriano; Maiorino, Luigi; Caratení, Giacomo; Gentile, Alfonso; Comella, Giuseppe.

In: Breast Cancer Research and Treatment, Vol. 49, No. 1, 1998, p. 13-26.

Research output: Contribution to journalArticle

Frasci, Giuseppe ; Comella, Pasquale ; D'Aiuto, Giuseppe ; Budillon, Alfredo ; Barbarulo, Deborah ; Thomas, Renato ; Capasso, Immacolata ; Casaretti, Rossana ; Daponte, Antonio ; Caponigro, Francesco ; Gravina, Adriano ; Maiorino, Luigi ; Caratení, Giacomo ; Gentile, Alfonso ; Comella, Giuseppe. / Weekly paclitaxel-cisplatin administration with G-CSF support in advanced breast cancer. A phase II study. In: Breast Cancer Research and Treatment. 1998 ; Vol. 49, No. 1. pp. 13-26.
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abstract = "Purpose: In a previous phase I study we found the MTDs of paclitaxel and cisplatin when given together weekly, with or without G-CSF support, in patients with advanced solid tumors. The present study was conducted to define the toxicity and efficacy of this regimen, when used with G-CSF support, in chemotherapy-naive or pretreated patients with advanced breast cancer, and to compare the antiproliferative activity of paclitaxel-cisplatin and paclitaxel-doxorubicin combinations on two human breast cancer cell lines. Methods: Patients with metastatic breast cancer received weekly paclitaxel (as a 3-hour IV infusion) at the dose of 85 mg/m2 (75 mg/m2 in pretreated women) followed by cisplatin (40 mg/m2) for a minimum of 6 weeks. An additional 6 weekly cycles were delivered in patients showing absence of documented disease progression after the first 6 weeks. After the 12th cycle only patients who had shown a substantial tumor shrinkage received 6 further cycles. G-CSF 5 μg/kg was also given, SC on days 3 to 5 of each week, for the whole duration of chemotherapy. The combination of paclitaxel with cisplatin or doxorubicin was also tested in vitro on two breast cancer cell lines (MCF-7 and MDAMB-231). Results: Forty-three women with metastatic breast cancer entered this trial between June 1995 and January 1997. Twenty-seven patients were previously untreated for their metastatic disease (but 23 had previously received adjuvant chemotherapy). The dominant site of disease involvement was visceral in 23, bone in 13, and soft tissues in 7 patients. Seven complete and 15 partial responses were observed in unpretreated patients, while no complete and 6 partial responses were achieved in the pretreated population. The overall response rate, assessed on an 'intent to treat' basis, was 81{\%} (26{\%} CRs) in patients unpretreated for metastatic disease and 37{\%} in those who had received one or more previous chemotherapy regimens. Eighteen responder patients had previously received anthracyclines either as adjuvant chemotherapy (12) or in the treatment of metastatic disease (6). At a median potential follow-up of 12 (range, 3-21) months, 14/27 unpretreated and 12/16 pretreated patients had shown disease progression. The median time to treatment failure was 13 and 7 months, respectively, in the 2 subgroups. The 1-year survival probability was 95{\%} in unpretreated patients. The treatment showed a moderate toxicity in both subgroups of patients. Both hematological toxicity and peripheral neuropathy occurred more frequently in pretreated patients. Treatment-related deaths did not occur, and severe myelosuppression was observed only in pretreated patients with massive liver involvement. Delays in chemotherapy administration were very uncommon, especially during the first 6 treatment cycles, and the average actually delivered dose intensity exceeded 90{\%} in unpretreated patients. The in vitro data on MCF-7 and MDA-MB-231 human breast cancer cell lines showed that exposure to the combination of cisplatin and paclitaxel produced a tumor cell killing similar to that achievable with equivalent concentrations of doxorubicin and paclitaxel. Conclusions: Weekly paclitaxel and cisplatin with G-CSF support is an active and particularly well tolerated treatment for patients with either unpretreated or pretreated metastatic breast cancer. This approach seems quite effective also in patients relapsing after anthracycline-based adjuvant chemotherapy. In view of the negligible hematological toxicity associated with this regimen, further clinical trials testing the addition of non cross-resistant drugs to this combination should be performed.",
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T1 - Weekly paclitaxel-cisplatin administration with G-CSF support in advanced breast cancer. A phase II study

AU - Frasci, Giuseppe

AU - Comella, Pasquale

AU - D'Aiuto, Giuseppe

AU - Budillon, Alfredo

AU - Barbarulo, Deborah

AU - Thomas, Renato

AU - Capasso, Immacolata

AU - Casaretti, Rossana

AU - Daponte, Antonio

AU - Caponigro, Francesco

AU - Gravina, Adriano

AU - Maiorino, Luigi

AU - Caratení, Giacomo

AU - Gentile, Alfonso

AU - Comella, Giuseppe

PY - 1998

Y1 - 1998

N2 - Purpose: In a previous phase I study we found the MTDs of paclitaxel and cisplatin when given together weekly, with or without G-CSF support, in patients with advanced solid tumors. The present study was conducted to define the toxicity and efficacy of this regimen, when used with G-CSF support, in chemotherapy-naive or pretreated patients with advanced breast cancer, and to compare the antiproliferative activity of paclitaxel-cisplatin and paclitaxel-doxorubicin combinations on two human breast cancer cell lines. Methods: Patients with metastatic breast cancer received weekly paclitaxel (as a 3-hour IV infusion) at the dose of 85 mg/m2 (75 mg/m2 in pretreated women) followed by cisplatin (40 mg/m2) for a minimum of 6 weeks. An additional 6 weekly cycles were delivered in patients showing absence of documented disease progression after the first 6 weeks. After the 12th cycle only patients who had shown a substantial tumor shrinkage received 6 further cycles. G-CSF 5 μg/kg was also given, SC on days 3 to 5 of each week, for the whole duration of chemotherapy. The combination of paclitaxel with cisplatin or doxorubicin was also tested in vitro on two breast cancer cell lines (MCF-7 and MDAMB-231). Results: Forty-three women with metastatic breast cancer entered this trial between June 1995 and January 1997. Twenty-seven patients were previously untreated for their metastatic disease (but 23 had previously received adjuvant chemotherapy). The dominant site of disease involvement was visceral in 23, bone in 13, and soft tissues in 7 patients. Seven complete and 15 partial responses were observed in unpretreated patients, while no complete and 6 partial responses were achieved in the pretreated population. The overall response rate, assessed on an 'intent to treat' basis, was 81% (26% CRs) in patients unpretreated for metastatic disease and 37% in those who had received one or more previous chemotherapy regimens. Eighteen responder patients had previously received anthracyclines either as adjuvant chemotherapy (12) or in the treatment of metastatic disease (6). At a median potential follow-up of 12 (range, 3-21) months, 14/27 unpretreated and 12/16 pretreated patients had shown disease progression. The median time to treatment failure was 13 and 7 months, respectively, in the 2 subgroups. The 1-year survival probability was 95% in unpretreated patients. The treatment showed a moderate toxicity in both subgroups of patients. Both hematological toxicity and peripheral neuropathy occurred more frequently in pretreated patients. Treatment-related deaths did not occur, and severe myelosuppression was observed only in pretreated patients with massive liver involvement. Delays in chemotherapy administration were very uncommon, especially during the first 6 treatment cycles, and the average actually delivered dose intensity exceeded 90% in unpretreated patients. The in vitro data on MCF-7 and MDA-MB-231 human breast cancer cell lines showed that exposure to the combination of cisplatin and paclitaxel produced a tumor cell killing similar to that achievable with equivalent concentrations of doxorubicin and paclitaxel. Conclusions: Weekly paclitaxel and cisplatin with G-CSF support is an active and particularly well tolerated treatment for patients with either unpretreated or pretreated metastatic breast cancer. This approach seems quite effective also in patients relapsing after anthracycline-based adjuvant chemotherapy. In view of the negligible hematological toxicity associated with this regimen, further clinical trials testing the addition of non cross-resistant drugs to this combination should be performed.

AB - Purpose: In a previous phase I study we found the MTDs of paclitaxel and cisplatin when given together weekly, with or without G-CSF support, in patients with advanced solid tumors. The present study was conducted to define the toxicity and efficacy of this regimen, when used with G-CSF support, in chemotherapy-naive or pretreated patients with advanced breast cancer, and to compare the antiproliferative activity of paclitaxel-cisplatin and paclitaxel-doxorubicin combinations on two human breast cancer cell lines. Methods: Patients with metastatic breast cancer received weekly paclitaxel (as a 3-hour IV infusion) at the dose of 85 mg/m2 (75 mg/m2 in pretreated women) followed by cisplatin (40 mg/m2) for a minimum of 6 weeks. An additional 6 weekly cycles were delivered in patients showing absence of documented disease progression after the first 6 weeks. After the 12th cycle only patients who had shown a substantial tumor shrinkage received 6 further cycles. G-CSF 5 μg/kg was also given, SC on days 3 to 5 of each week, for the whole duration of chemotherapy. The combination of paclitaxel with cisplatin or doxorubicin was also tested in vitro on two breast cancer cell lines (MCF-7 and MDAMB-231). Results: Forty-three women with metastatic breast cancer entered this trial between June 1995 and January 1997. Twenty-seven patients were previously untreated for their metastatic disease (but 23 had previously received adjuvant chemotherapy). The dominant site of disease involvement was visceral in 23, bone in 13, and soft tissues in 7 patients. Seven complete and 15 partial responses were observed in unpretreated patients, while no complete and 6 partial responses were achieved in the pretreated population. The overall response rate, assessed on an 'intent to treat' basis, was 81% (26% CRs) in patients unpretreated for metastatic disease and 37% in those who had received one or more previous chemotherapy regimens. Eighteen responder patients had previously received anthracyclines either as adjuvant chemotherapy (12) or in the treatment of metastatic disease (6). At a median potential follow-up of 12 (range, 3-21) months, 14/27 unpretreated and 12/16 pretreated patients had shown disease progression. The median time to treatment failure was 13 and 7 months, respectively, in the 2 subgroups. The 1-year survival probability was 95% in unpretreated patients. The treatment showed a moderate toxicity in both subgroups of patients. Both hematological toxicity and peripheral neuropathy occurred more frequently in pretreated patients. Treatment-related deaths did not occur, and severe myelosuppression was observed only in pretreated patients with massive liver involvement. Delays in chemotherapy administration were very uncommon, especially during the first 6 treatment cycles, and the average actually delivered dose intensity exceeded 90% in unpretreated patients. The in vitro data on MCF-7 and MDA-MB-231 human breast cancer cell lines showed that exposure to the combination of cisplatin and paclitaxel produced a tumor cell killing similar to that achievable with equivalent concentrations of doxorubicin and paclitaxel. Conclusions: Weekly paclitaxel and cisplatin with G-CSF support is an active and particularly well tolerated treatment for patients with either unpretreated or pretreated metastatic breast cancer. This approach seems quite effective also in patients relapsing after anthracycline-based adjuvant chemotherapy. In view of the negligible hematological toxicity associated with this regimen, further clinical trials testing the addition of non cross-resistant drugs to this combination should be performed.

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KW - Chemotherapy

KW - Cisplatin

KW - Paclitaxel

KW - Weekly schedule

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