A Study of Herceptin (Trastuzumab) in Combination Chemotherapy in Patients With Metastatic or Locally Advanced Breast Cancer

Sperimentale: Trastuzumab, Myocet, Paclitaxel; Phase I

Participants received an initial loading dose of trastuzumab 4 milligrams per kilogram (mg/kg), intravenously (IV), over 1.5 hours during Week 1, followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression. Participants also received myocet, 40 mg/ square meter (m^2), IV, every 3 weeks, from Week 1; if no dose limiting toxicity (DLT) was observed in greater than or equal to (≥) two-thirds (2/3) of cohort for 2 treatment cycles, the dose was increased to 50 mg/m^2, IV, and continued for 6 cycles. Participants also received paclitaxel 60 mg/ m^2, IV, once per week, from Week 19; if no DLT was observed in ≥ 2/3 of cohort for 2 treatment cycles, the dose was increased to 70 mg/m^2, IV, and subsequently 80 mg/m^2, IV, and continued until disease progression.

Droga: trastuzumab

Initial loading does of 4 mg/kg IV, followed by 2 mg/kg IV weekly, until disease progression

Altri nomi:

• Herceptin

Droga: paclitaxel

60 mg/m^2 IV weekly; dose increased to 70 mg/m^2, and subsequently 80 mg/m^2, after 2 treatment cycles with no evidence of DLT until disease progression

Droga: Myocet

40 mg/m^2 IV weekly; dose increased to 50 mg/m^2 IV after 2 treatment cycles with no evidence of DLT for 6 cycles

Sperimentale: Trastuzumab, Myocet, Paclitaxel; Phase II

Participants received an initial loading dose of trastuzumab 4 mg/kg, IV, over 1.5 hours during Week 1, followed by 2 mg/kg, IV, over 30 minutes once per week from Week 2 to Week 52 or until disease progression. Participants also received myocet, 50 mg/m^2, IV, every 3 weeks, from Week 1 for 6 cycles. Participants also received paclitaxel 80 mg/m^2, IV, once per week, from Week 19 until disease progression.

Droga: trastuzumab

Initial loading does of 4 mg/kg IV, followed by 2 mg/kg IV weekly, until disease progression

Altri nomi:

• Herceptin

Droga: paclitaxel

60 mg/m^2 IV weekly; dose increased to 70 mg/m^2, and subsequently 80 mg/m^2, after 2 treatment cycles with no evidence of DLT until disease progression

Droga: Myocet

40 mg/m^2 IV weekly; dose increased to 50 mg/m^2 IV after 2 treatment cycles with no evidence of DLT for 6 cycles

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to World Health Organization (WHO) Handbook for Reporting Results of Cancer Treatment

For measurable disease, CR was defined as the disappearance of all clinically detectable disease determined by 2 observations not less than 4 weeks apart; and PR was defined as a 50 percent (%) decrease in the sum of the products of the 2 greatest diameters of all measurable lesions by 2 observations not less than 4 weeks apart, and no appearance of new lesions or progression of any lesion. For immeasurable disease, CR was defined as the complete disappearance of all known disease for at least 4 weeks; and PR was defined as an estimated decrease in tumor size of 50% or more for at least 4 weeks.

Time to Disease Progression - Percentage of Participants With an Event

Disease progression was defined as the time from the start of treatment to the date of the first recorded incident of disease progression, or the date of death due any cause. For measurable disease, disease progression was defined as a ≥25% increase in the sum of the products of diameters of 1 or more measurable lesions with a minimal area of greater than (>)2 square centimeters (cm^2), or the appearance of new lesions; and for malignant lesions with a minimal area of 2 cm^2, an increase of ≥1 cm^2. For immeasurable disease, disease progression was defined as the appearance of any new lesion not previously identified or an estimated increase of ≥50% in existent lesions.

Time to Disease Progression

The median time, in months, from the start of treatment to disease progression event.

Time to Treatment Response - Percentage of Participants With an Event

Treatment response was defined as the time from the start of treatment to the date of recorded CR or PR of measurable disease.

Time to Treatment Response

The median time, in months, from the start of treatment to treatment response event.

Duration of Response - Percentage of Participants With an Event

Duration of response was defined as the time from date CR was first recorded to the date progressive disease (PD) was first noted. For measurable disease, PD was defined as a ≥25% increase in the sum of the products of diameters of 1 or more measurable lesions with a minimal area of >2 cm^2, or the appearance of new lesions; and for malignant lesions with a minimal area of 2 cm^2, an increase of ≥1 cm^2. For immeasurable disease, PD was defined as the appearance of any new lesion not previously identified or an estimated increase of ≥50% in existent lesions.

Duration of Response

The median time, in months, from enrollment to duration of response event to Week 52.

Time to Therapy Failure - Percentage of Participants With an Event

Therapy failure was defined as the date of the start of therapy to the date of withdrawal due to adverse events, progressive disease/insufficient therapeutic response, death, failure to return, or refusal of treatment/lack of cooperation/withdrawal of consent. Participants were censored at the last dose of treatment if no event was recorded.

Time to Therapy Failure

The median time, in months, from treatment start to therapy failure event. Participants were censored at the last date of treatment if no event was recorded.

Overall Survival (OS) - Percentage of Participants With an Event

OS was defined as the time from the date of the start of treatment to the date of death or the last date the participant was known to be alive.

Overall Survival

The time, in months, from the start of treatment to OS event. The mean survival time and it's standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.