Abstract
Five hundred and twenty-one patients with ABC were randomized to receive PTX over 3-hr or 24-hr q 3 wks at an initial dose of 175
mg/m
2 (with escalation when possible). The pre-randomization strata were defined according to prior chemotherapy (CT): none, adjuvant CT only, CT for ABC. Two-thirds of the patients had prior anthracycline exposure; 24% of these were anthracycline resistant, i.e. progressing on or relapsing within 6 months of an anthracycline regimen.
The response rate was 29% in the 3-hr vs 32% in the 24-hr (
P
=
0.629). It was 28% in both arms among anthracycline pretreated patients. Among all patients, treatment over 24-hr resulted in a longer time to progression (TTP) (median 3.8 mos vs 4.6 mos:
P
=
0.021) and survival time (median 9.8 mosvs 13.4 mos;
P
=
0.021). This difference was not apparent after adjustment for prognostic factors, TTP:
P
=
0.081, survival:
P
=
0.099. Treatment was well tolerated as documented by the # of crs administered (median 6 (1–22+) vs 7 (1–21);
P
<
0.01). More patients in the 3-hr arm had their PTX dose escalated (65% in the 3-hr vs 33% in the 24-hr.
P
<
0.001), resulting in an increased dose intensity (62 vs 57
mg/m
2/wk;
P
<
0.001). The 2 treatment schedules were not equitoxic even after individual dose adjustments. The 24-hr infusion resulted in more severe hematologic (30% vs 79% grade IV neutropenia,
P
<
0.001; 1% vs 17% febrile neutropenia,
P
<
0.001), and GI toxicity (22% vs 45% mucositis,
P
<
0.001; 25% vs 41% diarrhea,
P
<
0.001). The 3-hr infusion with its higher dose intensity resulted in a higher incidence of peripheral neuropathy (78% vs 65%,
P
=
0.001). To evaluate the risk-benefit ratio associated with therapy, we retrospectively analyze the time to either progression or to clinically important adverse events (febrile neutropenia, severe hypersensitivity reaction, and severe neuropathy), and found no statistically significant difference between the two arms (median 3.3 mos vs 3.4 mos;
P
=
0.243). In the palliative setting, the 24-hr infusion of PTX had some efficacy advantage, but did not result in a significant increase in patient benefit as compared to the 3-hr infusion. This trial confirms the activity of PTX in the treatment of ABC pts, including anthracycline pretreated patients.