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Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

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Abstract

Background

A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2.

Patients and methods

Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m2) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD).

Results

Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035).

Conclusion

Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+.

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Authors and Affiliations

  1. Medical Oncology Division, “San Filippo Neri” Hospital, Unità Operativa Complessa di Oncologia Medica, Azienda Complesso Ospedaliero di Rilevanza Nazionale “S. Filippo Neri “, Via G. Martinotti, 20-00135, Rome, Italy

    Giampietro Gasparini, Alessandro Morabito, Francesco Torino & Livia De Sio

  2. Regional Center for the Study of Biological Markers of Malignancy, General Regional Hospital, ULSS 12, Venice, Italy

    Massimo Gion & Matelda Zancan

  3. National Cancer Institute Milan, Unit of Medical Statistics and Biometry, Milan, Italy

    Luigi Mariani

  4. Medical Oncology Division “A”, Istituti Fisioterapici Ospedalieri “Regina Elena”, Rome, Italy

    Paola Papaldo & Francesco Cognetti

  5. Centro di Riferimento Oncologico, Aviano, Italy

    Diana Crivellari & Antonella Spada

  6. Presidio Ospedaliero di Paola, Paola, Italy

    Gianfranco Filippelli & Antonio Caputo

  7. Cattedra di Oncologia, Università di Modena, Modena, Italy

    Vittorio Silingardi

  8. Hoffmann-La Roche, Milano, Italy

    Antonio Lambiase

  9. Ospedale Morgagni – Pierantoni, Forlì, Italy

    Dino Amadori

Authors
  1. Giampietro Gasparini
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  2. Massimo Gion
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  3. Luigi Mariani
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  4. Paola Papaldo
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  5. Diana Crivellari
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  6. Gianfranco Filippelli
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  7. Alessandro Morabito
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  9. Francesco Torino
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  10. Antonella Spada
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  11. Matelda Zancan
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  12. Livia De Sio
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  13. Antonio Caputo
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  14. Francesco Cognetti
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  15. Antonio Lambiase
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  16. Dino Amadori
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Corresponding author

Correspondence to Giampietro Gasparini.

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Gasparini, G., Gion, M., Mariani, L. et al. Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer. Breast Cancer Res Treat 101, 355–365 (2007). https://doi.org/10.1007/s10549-006-9306-9

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  • DOI: https://doi.org/10.1007/s10549-006-9306-9

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