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.

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.

Advanced breast cancer: a phase II trial with gemcitabine.

1995 ◽  
Vol 13 (11) ◽  
pp. 2731-2736 ◽  
Author(s):  
J Carmichael ◽  
K Possinger ◽  
P Phillip ◽  
M Beykirch ◽  
H Kerr ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Advanced Breast ◽  
World Health ◽  
Survival Duration ◽  
Hematologic Toxicity ◽  
Who Grade ◽  
The Mean

PURPOSE In this phase II study, the efficacy and tolerability of gemcitabine were studied in 44 patients with locally advanced or metastatic breast cancer. PATIENTS AND METHODS Of 40 patients assessable for response, 14 were chemotherapy-naive, seven had received adjuvant chemotherapy, and 19 had received one prior chemotherapy regimen for metastatic disease. Gemcitabine was administered as a 30-minute intravenous infusion once a week for 3 weeks followed by a 1-week rest every 4 weeks. The mean number of completed cycles administered was 2.7 and the mean dosage delivered was 725 mg/m2 per injection. Eighty-one percent of doses were delivered as scheduled. RESULTS There were three complete responses and seven partial responses, for an overall response rate of 25.0% (95% confidence interval [CI], 12.7% to 41.2%). Four patients were not assessable for efficacy (one had insufficient therapy, two had no bidimensionally measurable disease, and one had neither). All responses were independently validated by an external oncology review board. Responses were observed early in treatment, with a median time to response of 1.9 months. The median survival duration for all 40 assessable patients was 11.5 months. Hematologic toxicity was generally mild, with World Health Organization (WHO) grade 3 and 4 leukopenia occurring in 6.8% and 2.3% of patients and neutropenia in 23.3% and 7.0%, of patients, respectively. The only other grade 4 toxicities were infection and nausea and vomiting in one patient each. One patient was withdrawn due to shortness of breath, possibly drug-related. Flu-like symptoms, which were mild, transient, and treatable with acetominophen, were reported in 6.8% of patients. Only one patient developed alopecia of severity greater than WHO grade 2. CONCLUSION In view of the single-agent activity seen in advanced breast cancer, modest toxicity profile, and novel mechanism of action, gemcitabine deserves evaluation in breast cancer and is an ideal candidate for combination therapy.

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

Phase II trial of pegylated liposomal doxorubicin (Caelyx™) plus Gemcitabine in chemotherapeutically pretreated patients with advanced breast cancer

2007 ◽  
Vol 46 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Herbert Ulrich-Pur ◽  
Gabriela V. Kornek ◽  
Karin Haider ◽  
Werner Kwasny ◽  
Thomas Payrits ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Phase Ii Trial ◽  
Pegylated Liposomal Doxorubicin ◽  
Advanced Breast ◽  
Pretreated Patients

PALOMAGE, a French real-world cohort of elderly women beyond age 70 with advanced breast cancer receiving palbociclib: Baseline characteristics and safety evaluation.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1012-1012
Author(s):  
Philippe Caillet ◽  
Marina Pulido ◽  
Etienne Brain ◽  
Claire Falandry ◽  
Isabelle Desmoulins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Real World ◽  
Older Patients ◽  
Systemic Treatment ◽  
Safety Data ◽  
Real Life ◽  
Advanced Breast ◽  
Baseline Characteristics ◽  
Grade 3

1012 Background: Advanced breast cancer (ABC) is common in older patients, resulting from the high incidence of breast cancer beyond age 70. This population is often limited in clinical trials. Endocrine therapy (ET) combined with a CDK4/6 inhibitor is the standard of care in ABC overexpressing hormonal receptors (HR+). Data specific to older patients are scarce in the literature, deserving further research. Methods: PALOMAGE is an ongoing French prospective study evaluating palbociclib (PAL) + ET in real life setting in women aged ≥70 with HR+ HER2- ABC, split in 2 cohorts: ET sensitive patients with no prior systemic treatment for ABC (cohort A), and ET resistant patients and/or with prior systemic treatment for ABC (cohort B). Data collected include clinical characteristics, quality of life (EORTC QLQ-C30 and ELD14) and geriatric description [G8 and Geriatric-COre DatasEt (G-CODE)]. This analysis reports on baseline characteristics and safety data for the whole population. Results: From 10/2018 to 10/2020, 400 and 407 patients were included in cohort A and B, respectively. The median age was 79 years (69-98), 15.1% with an age > 85. ECOG performance status (PS) was ≥2 in 17.9% patients, 68.3% had a G8 score ≤14 suggesting frailty, 32.1% had bone only metastasis, and 44% had visceral disease. 35.8% of patients in cohort B had no prior treatment for ABC. Safety data were available for 787 patients. The median follow-up was 6.7 months (IC95% = 6.1-7.6). At start of treatment, full dose of PAL (125 mg) was used in 76% of the patients: 62.6%, 68.7% and 71.6% of patients aged ≥ 80, those with ECOG PS ≥2 and those with a G8 score ≤14, respectively. In the safety population, 70% had ≥1 adverse event (AE), including 43.1% grade 3/4 AE, and 22.9% ≥ 1 serious AE. Most frequent AE reported were neutropenia (43.2%), anemia (17.5%), asthenia (16.3%) and thrombocytopenia (13.6%). Grade 3/4 neutropenia was observed in 32.3% of patients, with febrile neutropenia in 1.1%. Grade 3/4 AE PAL-related were reported in 40.1%, 31.4% of patients aged < 80, ≥80, respectively. Regarding PAL, 23.4% of patients had a dose reduction and 41.8% had a temporary or permanent discontinuation due to AE. Safety data were similar in both cohorts. Geriatric data and impact on safety will be presented. Conclusions: PALOMAGE is a unique large real-world cohort focusing on older patients treated with PAL in France. These preliminary data do not suggest any new safety signal, matching data derived from PALOMA trials. The occurrence of less grade3/4 AE related to PAL in patients aged 80 and beyond might reflect the 30% decrease of PAL dose upfront. Effectiveness analyses are eagerly awaited. Clinical trial information: EUPAS23012 .

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