Phase II Study of the Efficacy and Tolerability of Two Dosing Regimens of the Farnesyl Transferase Inhibitor, R115777, in Advanced Breast Cancer

2003 ◽  
Vol 21 (13) ◽  
pp. 2492-2499 ◽  
Author(s):  
Stephen R.D. Johnston ◽  
Tamas Hickish ◽  
Paul Ellis ◽  
Stephen Houston ◽  
Lloyd Kelland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Hematologic Toxicity ◽  
Farnesyl Transferase ◽  
Farnesyl Transferase Inhibitor ◽  
Grade 3

Purpose: R115777 is an orally active farnesyl transferase inhibitor that specifically blocks farnesylation of proteins involved in growth-factor–dependent cell-signal–transduction pathways. We conducted a phase II study in 76 patients with advanced breast cancer. Patients and Methods: Two cohorts of patients were recruited sequentially. The first cohort (n = 41) received a continuous dosing [CD] regimen of R115777 400 or 300 mg bid. The second cohort (n = 35) received 300 mg bid in a cyclical regimen of 21 days of treatment followed by 7 days of rest (intermittent dosing [ID]). Results: In the CD cohort, four patients (10%) had a partial response (PR) and six patients (15%) had stable disease at ≥ 24 weeks (SD). In the ID cohort, five patients (14%) had a PR and three patients (9%) had prolonged SD. The first six patients in the CD cohort treated at 400 mg bid all developed grade 3 to 4 neutropenia, so the subsequent 35 patients were treated at 300 mg bid. The incidence of hematologic toxicity was significantly lower in the ID than in the CD (300-mg bid) cohort: grade 3 to 4 neutropenia (14% v 43%; P = .016) and grade 3 to 4 thrombocytopenia (3% v 26%; P = .013). One patient in the ID cohort developed grade 2 to 3 neurotoxicity compared with 15 patients in the CD cohort (3% v 37%; P = .0004). Conclusion: The farnesyl transferase inhibitor R115777 has demonstrated clinical activity in patients with metastatic breast cancer, and the ID regimen has a significantly improved therapeutic index compared with the CD regimen.

Multicenter Phase II Study of a 28-Day Regimen of Orally Administered Eniluracil and Fluorouracil in the Treatment of Patients With Anthracycline- and Taxane-Resistant Advanced Breast Cancer

2002 ◽  
Vol 20 (4) ◽  
pp. 987-993 ◽  
Author(s):  
Edgardo Rivera ◽  
Linda Sutton ◽  
Bruce Colwell ◽  
Mark Graham ◽  
Debra Frye ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Median Duration ◽  
Dihydropyrimidine Dehydrogenase ◽  
Advanced Breast ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Grade 3

PURPOSE: Eniluracil (776C85), a potent inactivator of dihydropyrimidine dehydrogenase, allows fluorouracil (5-FU) to be administered orally on a schedule that simulates continuous-infusion 5-FU. The primary objective of this study was to estimate the objective tumor response rate of orally administered eniluracil and 5-FU in the treatment of anthracycline- and taxane-resistant advanced breast cancer. PATIENTS AND METHODS: Patients with anthracycline- and taxane-resistant advanced breast cancer were enrolled onto this open-label, phase II, multicenter study. Patients received orally administered 5-FU 1.0 mg/m2 with eniluracil given in a 10:1 ratio (eniluracil:5-FU) twice daily for the first 28 days of each 35-day cycle. RESULTS: Eighty-four patients were enrolled. Eight partial responses were observed in 84 patients (10%; 95% confidence interval [CI], 4.2% to 17.9%), and 20 patients (24%) had stable disease. The median duration of partial response was 20.1 weeks (95% CI, 12 to 26.7 weeks). The median duration of progression-free survival and overall survival for all patients was 9.9 weeks and 40.4 weeks, respectively. Most adverse events were grade 1 or 2 in intensity. Diarrhea, nausea, malaise/fatigue, vomiting, and mucositis were the most common treatment-related nonhematologic adverse events. The most frequently occurring grade 3 or 4 treatment-related adverse events were malaise/fatigue and diarrhea, occurring in 17% and 7% of patients, respectively. The incidence of grade 3 or 4 hematologic toxicity was low. Grade 3 or 4 hyperbilirubinemia occurred in 17% of patients. CONCLUSION: Eniluracil–5-FU has modest antitumor activity and an acceptable safety profile in anthracycline- and taxane-resistant breast cancer. Treatment was convenient, and patient compliance was high.

Low-Dose Oral Fluorouracil With Eniluracil as First-Line Chemotherapy Against Advanced Breast Cancer: A Phase II Study

2000 ◽  
Vol 18 (12) ◽  
pp. 2378-2384 ◽  
Author(s):  
Ian E. Smith ◽  
Stephen R. D. Johnston ◽  
Mary E. R. O’Brien ◽  
Tamas F. Hickish ◽  
Richard H. de Boer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Low Dose ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
First Line ◽  
Dose Oral

PURPOSE: Eniluracil (776C85) is an effective inactivator of dihydropyrimidine dehydrogenase that allows continuous low-dose oral fluorouracil (5-FU) to be given with predicable oral bioavailability. We have assessed this as first-line oral chemotherapy for patients with advanced/metastatic breast cancer. PATIENTS AND METHODS: Patients with histologically proven, locally advanced or metastatic breast cancer without previous chemotherapy for advanced disease were entered onto this open-label phase II study. Patients received oral 5-FU 1.0 mg/m2 with eniluracil 10 mg/m2, both given twice daily for the first 28 days of each 35-day cycle, continuing until disease progression or unmanageable toxicity. RESULTS: Thirty-three patients were entered, with a median age of 53 years. Sixteen partial responses were seen in twenty-nine assessable patients (55%; 95% confidence interval, 37% to 73%), including responses in four (40%) out of 10 patients who had received prior adjuvant 5-FU. Seven patients had stable disease for at least 3 months with symptom improvement. Median response duration was 14 months (range, 10 to 18+ months). Toxicity was low. There were only two episodes of drug-related grade 3 nonhematologic toxicity (diarrhea and infection), and only 6%, 3%, and 3% of patients developed granulocytopenia, thrombocytopenia, and neutropenic sepsis, respectively. Mild (grade 1/2) diarrhea occurred in 39% of patients, hand-foot syndrome in 15%, nausea in 27%, and mucositis in 18%. Toxicity-associated delay and dose reduction occurred in only 2% and 5% of courses, respectively. CONCLUSION: First-line treatment with the combination of oral 5-FU and eniluracil has high activity in patients with advanced breast cancer comparable with the most active conventional cytotoxic agents but with strikingly less toxicity.

Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial.

1997 ◽  
Vol 15 (10) ◽  
pp. 3185-3191 ◽  
Author(s):  
M R Ranson ◽  
J Carmichael ◽  
K O'Byrne ◽  
S Stewart ◽  
D Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Active Agent ◽  
Metastatic Breast ◽  
Skin Toxicity ◽  
Advanced Breast ◽  
Multicenter Phase ◽  
Stage Iv Breast Cancer ◽  
Grade 3

PURPOSE A multicenter phase II study to determine the activity and toxicity of Caelyx (Doxil; Sequus Pharmaceuticals Inc, Menlo Park, CA) in patients with metastatic breast cancer. PATIENTS AND METHODS Seventy-one patients with stage IV breast cancer were treated with Caelyx at doses of 45 to 60 mg/m2 every 3 to 4 weeks for a maximum of six cycles. Twenty-eight patients had received prior chemotherapy with a nonanthracycline regimen. Fifty-two patients had disease at multiple sites. Hepatic and pulmonary disease were the predominant metastatic site in 50 patients. Response was assessable in 64 cases. RESULTS Sixteen patients achieved a partial response and a complete response (overall response rate, 31%; (95% confidence interval, 20% to 43%). Twenty patients (31%) had stable disease on treatment. Neutropenia > or = grade 3 occurred in 10% of cycles (27% of patients) and mucositis > or = grade 3 in 10% of cycles (32% of patients). Significant alopecia was rare and routine prophylactic antiemetics were not required. At doses of 60 mg/m2 every 3 weeks, seven of 13 patients had > or = grade 3 skin toxicity; overall, this toxicity complicated 25% of treatment cycles. The incidence of > or = grade 3 skin toxicity was greatly reduced at doses of 45 mg/m2 every 4 weeks, occurring in five of 32 patients and affecting only 5% of 126 treatment cycles. CONCLUSION Caelyx is an active agent in advanced breast cancer with a safety profile that differs markedly from nonliposomal doxorubicin. A regimen of 45 mg/m2 every 4 weeks was well tolerated in this cohort of women with advanced poor-prognosis breast cancer. The mild myelosuppression seen with this regimen would favor its use in combination chemotherapy.

Megestrol acetate: Phase II study of a single daily administration in advanced breast cancer

1990 ◽  
Vol 17 (1) ◽  
pp. 51-54 ◽  
Author(s):  
Paolo Pronzato ◽  
Fulvio Brema ◽  
Domenico Amoroso ◽  
Gianfilippo Bertelli ◽  
Pier Franco Conte ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Breast ◽  
Megestrol Acetate ◽  
Daily Administration

Bromocriptin (B) and lanreotide (L) in advanced breast cancer: A phase II study

1993 ◽  
Vol 29 ◽  
pp. S84 ◽  
Author(s):  
J. Bonneterre ◽  
J.M. Plon ◽  
A. Adenis ◽  
J.P. Peyrat ◽  
S. Henane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Breast

Centchroman—a non-steroidal anti-cancer agent for advanced breast cancer: Phase-II study

1989 ◽  
Vol 43 (5) ◽  
pp. 781-783 ◽  
Author(s):  
N. C. Misra ◽  
P. K. Nigam ◽  
Ruby Gupta ◽  
A. K. Agarwal ◽  
V. P. Kamboj
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Breast ◽  
Anti Cancer ◽  
Cancer Agent

A phase II study of losoxantrone (dup 941) in advanced breast cancer

1993 ◽  
Vol 29 ◽  
pp. S78
Author(s):  
W. Ten Bokkel Muinink ◽  
M. Moore ◽  
I. Smith ◽  
T. Vandenberg ◽  
M. Barbu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Breast

Vinorelbine as second line treatment in anthracycline pre-treated advanced breast cancer patients: A phase II study

1993 ◽  
Vol 29 ◽  
pp. S82 ◽  
Author(s):  
L. Dogliotti ◽  
G. Gorzegno ◽  
M.G. Bau ◽  
A. Farris ◽  
C. Bumma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Breast ◽  
Line Treatment ◽  
Second Line ◽  
Breast Cancer Patients
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