A feasibility study evaluating docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer

BACKGROUND AND PURPOSE: Docetaxel is an active agent in the treatment of metastatic breast cancer. We evaluated the feasibility of docetaxel-based sequential and combination regimens as adjuvant therapies for patients with node-positive breast cancer. PATIENTS AND METHODS: Three consecutive groups of patients with node-positive breast cancer or locally-advanced disease, aged < or = 70 years, received one of the following regimens: a) sequential A-->T-->CMF: doxorubicin 75 mg/m2 q 3 weeks x 3, followed by docetaxel 100 mg/m2 q 3 weeks x 3, followed by i.v. CMF days 1 + 8 q 4 weeks x 3; b) sequential accelerated A-->T-->CMF: A and T were administered at the same doses q 2 weeks; c) combination therapy: doxorubicin 50 mg/m2 + docetaxel 75 mg/m2 q 3 weeks x 4, followed by CMF x 4. When indicated, radiotherapy was administered during or after CMF, and tamoxifen started after the end of CMF. RESULTS: Seventy-nine patients have been treated. Median age was 48 years. A 30% rate of early treatment discontinuation was observed in patients receiving the sequential accelerated therapy (23% during A-->T), due principally to severe skin toxicity. Median relative dose-intensity was 100% in the three treatment arms. The incidence of G3-G4 major toxicities by treated patients, was as follows: skin toxicity a: 5%; b: 27%; c: 0%; stomatitis a: 20%; b: 20%; c: 3%. The incidence of neutropenic fever was a: 30%; b: 13%; c: 48%. After a median follow-up of 18 months, no late toxicity has been reported. CONCLUSIONS: The accelerated sequential A-->T-->CMF treatment is not feasible due to an excess of skin toxicity. The sequential non accelerated and the combination regimens are feasible and under evaluation in a phase III trial of adjuvant therapy.

3-year results of docetaxel-based sequential and combination regimens in the adjuvant therapy of node-positive breast cancer: a pilot study.

BACKGROUND: Docetaxel has proven efficacy in metastatic breast cancer. In this pilot study, we explored the efficacy/feasibility of docetaxel-based sequential and combination regimens as adjuvant therapy of node-positive breast cancer. PATIENTS AND METHODS: From March 1996 till March 1998, four consecutive groups of patients with stages II and III breast cancer, aged < or = 70 years, received one of the following regimens: a) sequential Doxorubicin (A) --> Docetaxel (T) --> CMF (Cyclophosphamide+Methotrexate+5-Fluorouracil): A 75 mg/m q 3 wks x 3, followed by T100 mg/m2 q 3 wks x 3, followed by i.v. CMF Days 1+8 q 4 wks x 3; b) sequential accelerated A --> T --> CMF: A and T administered at the same doses q 2 wks with Lenograstin support; c) combination therapy: A 50 mg/m2 + T 75 mg/m2 q 3 wks x 4, followed by CMF x 4; d) sequential T --> A --> CMF: T and A, administered as in group a), with the reverse sequence. When indicated, radiotherapy was administered during or after CMF, and Tamoxifen after CMF. RESULTS: Ninety-three patients were treated. The median age was 48 years (29-66) and the median number of positive axillary nodes was 6 (1-25). Tumors were operable in 94% and locally advanced in 6% of cases. Pathological tumor size was >2 cm in 72% of cases. There were 21 relapses, (18 systemic, 3 locoregional) and 11 patients (12%) have died from disease progression. At median follow-up of 39 months (6-57), overall survival (OS) was 87% (95% CI, 79-94%) and disease-free survival (DFS) was 76% (95% CI, 67%-85%). CONCLUSION: The efficacy of these docetaxel-based regimens, in terms of OS and DFS, appears to be at least as good as standard anthracycline-based adjuvant chemotherapy (CT), in similar high-risk patient populations.

A dose-finding study of lanreotide (a somatostatin analog) in patients with colorectal carcinoma

BACKGROUND. Laboratory data suggest that insulin-like growth factor-1 (IGE-1) may stimulate the growth of different human tumors. At least in acromegalic patients, somatostatin (SMS) analogs, such as lanreotide, suppress the serum levels of growth hormone (GH) and IGE-1. METHODS. To evaluate the tolerability and biologic activity of different doses of lanreotide in patients with advanced colorectal carcinoma, consecutive groups of 3 patients each were subcutaneous treated with lanreotide at doses of 1, 2, 3, 4, 5, or 6 mg three times a day for 2 months. In the event of Grade 3 side effects, 3 additional patients were treated with the same dose before the next dose escalation. Serum samples were obtained on Days 0, 15, 30, and 60 for serum GH, IGF-1, and lanreotide assessment. RESULTS. Twenty-four patients were enrolled and all were evaluable. Except for the 3 and 6 mg doses, for which the observation of a Grade 3 side effect required that an additional three patients be treated, it was sufficient to treat 3 patients at each dose. The overall incidence of side effects was as follows: changes in bowel habits, 83%; abdominal cramps, 79%; diarrhea, 17%; vomiting, 17%; nausea, 21%; steatorrhea, 78%; hyperglycemia, 35%; laboratory hypothyroidism, 39%; gallstones, 13%; and weight loss, 17%. No evidence of an increase in the incidence, intensity, or duration of side effects was observed with dose escalation. Serum IGF-1 levels were as follows: Day 13: 63%, 60%, and 67% of the baseline values for the low (12 mg), intermediate (3-4 mg), and high (5- 6 mg) dose groups, respectively; Day 30: 63%, 59%, and 51%, respectively; and Day 60: 73%, 69%, and 47%, respectively. Serum lanreotide levels declined during treatment in all of the dose groups (90 ng/mL on Day 15, and 35 ng/mL on Day 60 for the 5-6 mg group; 10 ng/mL on Day 15, and 1.5 ng/mL on Day 60 for the 1-2 mg group). No antitumor activity or tumor marker reduction was observed. CONCLUSIONS. No increase in toxicity was observed when subcutaneous lanreotide doses were escalated to 6 mg three times a day for 2 months. The highest doses seemed to maintain reduced serum IGF-1 levels; with the lowest doses, a 'rebound' in serum IGF-1 levels was observed during treatment. Nevertheless, intermittent subcutaneous injections do not ensure constant serum drug concentrations over time.