Cisplatin and VP16 in Metastatic Breast Carcinoma as a Third-Line Chemotherapy: A Randomized Study Comparing Low versus High Doses of Cisplatin

1995 ◽  
Vol 81 (4) ◽  
pp. 241-244 ◽  
Author(s):  
Guido Ceci ◽  
Giancarlo Bisagni ◽  
Giorgio Cocconi ◽  
Carmelina Rodinò ◽  
Virginio Belsanti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Low Dose ◽  
Objective Response ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
High Dose ◽  
Severe Toxicity ◽  
Third Line ◽  
Line Chemotherapy

Aims and background The study was designed to define the activity of the combination of cisplatin and etoposide as third-line chemotherapy for advanced breast cancer and to investigate the role of the dosage of cisplatin on the effectiveness of the combination. Methods Ninety-five eligible patients with advanced breast cancer who had failed or relapsed on two previous lines of chemotherapy were randomized to receive cisplatin at a high dose (100 mg/m2 i.v. day 1, arm A) or a low dose (60 mg/m2 day 1, arm B), combined with etoposide (100 mg/m2 i.v. days 4, 6 and 8). Cycles were repeated every 3 weeks. Results Of the 78 patients evaluable for response (39 in arm A and 39 in arm B), 9 (12%) showed complete or partial response, 5 (13%) in the high-dose arm and 4 (10%) in the low-dose arm. One complete response was seen in the high-dose arm and none in the low-dose arm. The only 2 patients with brain involvement showed an objective response (one CR in arm A and one PR in arm B). Median time to progression was 14 weeks in arm A and 10 weeks in arm B, median duration of remission 28 and 34 weeks, and survival 36 and 35 weeks, respectively. The differences were not significant. As expected, the patients in the high-dose arm experienced more severe toxicity. One toxic death was observed in each arm due to sepsis in agranulocytosis. The difference was statistically significant regarding nausea and vomiting. Neurotoxicity and ototoxicity were not relevant problems in this patient setting. Conclusions Considering the very poor prognostic factors presented by these patients, the combination showed a certain activity, and further evaluation in earlier stages of disease is warranted. A particular responsiveness on brain metastases is suggested. The dose of cisplatin was not proven to be of significant importance.

Multicenter phase II efficacy trial of toremifene in tamoxifen-refractory patients with advanced breast cancer.

1993 ◽  
Vol 11 (2) ◽  
pp. 345-350 ◽  
Author(s):  
C L Vogel ◽  
I Shemano ◽  
J Schoenfelder ◽  
R A Gams ◽  
M R Green
Keyword(s):  
Breast Cancer ◽  
Treatment Failure ◽  
Advanced Breast Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Objective Response ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Cross Resistance ◽  
High Dose

PURPOSE To explore further the efficacy of high-dose toremifene in patients with advanced breast cancer who had failed to respond to tamoxifen or whose disease had progressed on tamoxifen. PATIENTS AND METHODS One hundred two perimenopausal or postmenopausal women with metastatic breast cancer refractory to tamoxifen were entered onto a phase II clinical trial of toremifene at a dose of 200 mg/d. The study patients consisted of 28 primarily refractory patients; 43 patients who had relapsed after a prior tamoxifen response; and 31 patients who had relapsed while receiving adjuvant tamoxifen. This was a heavily pretreated group of patients, with 65% having failed chemotherapeutic attempts and 72% having failed two or more hormonal therapies. Forty-nine percent of patients had visceral dominant disease. RESULTS The objective response rate was 5% (95% confidence interval [CI], 3% to 7%). The median time to treatment failure (TTF) was 10.9 months for the five responders. An additional 23% of patients had stable disease for a median TTF of 7.8 months, whereas the patients who experienced treatment failure had a median TTF of 2.1 months. Whether those patients with stable disease derived clinical benefit or simply had slow progression in an intrinsically indolent disease presentation is uncertain. Common toxicities were generally mild and similar to those encountered with tamoxifen. CONCLUSION We conclude that there is major cross-resistance between tamoxifen and toremifene and that only occasional tamoxifen-refractory patients will have objective responses to toremifene.

Vinorelbine as first-line chemotherapy for metastatic breast carcinoma.

1994 ◽  
Vol 12 (2) ◽  
pp. 336-341 ◽  
Author(s):  
A Romero ◽  
M G Rabinovich ◽  
C T Vallejo ◽  
J E Perez ◽  
R Rodriguez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Breast Carcinoma ◽  
Objective Response ◽  
Metastatic Breast ◽  
Survival Duration ◽  
Severe Toxicity ◽  
First Line ◽  
Metastatic Breast Carcinoma ◽  
Line Chemotherapy

PURPOSE A phase II trial was performed to evaluate the efficacy and toxicity of vinorelbine (VNB) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS Between August 1991 and February 1993, 45 patients with metastatic breast cancer were entered onto the study. Therapy consisted of VNB 30 mg/m2 diluted in 500 mL of normal saline administered as a 1-hour intravenous infusion. Injections were repeated weekly until evidence of progressive disease (PD) or severe toxicity developed. RESULTS One patient was considered not assessable for response. An objective response (OR) was observed in 18 of 44 patients (41%; 95% confidence interval, 26% to 56%). Three patients (7%) had a complete response (CR) and 15 (34%) had a partial response (PR). The median time to treatment failure for the entire group was 6 months (range, 1 to 15), and the median duration of response was 9 months (range, 1 to 15). The median survival duration has not been reached yet. There were no treatment-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (78%) and was grade 3 or 4 in 16 (36%). Phlebitis was observed in 19 of 29 patients (66%) who did not have central implantable venous systems. Fifteen patients (33%) developed peripheral neurotoxicity. Myalgia occurred in 20 patients (44%). CONCLUSION VNB is an active drug against metastatic breast cancer with moderate toxicity, which justifies further evaluation in association with other agents.

scholarly journals Second-line chemotherapy with long-term low-dose oral etoposide in patients with advanced breast cancer

1995 ◽  
Vol 34 (2) ◽  
pp. 185-189 ◽  
Author(s):  
M. Bontenbal ◽  
A. S. Th. Planting ◽  
J. Verweij ◽  
R. de Wit ◽  
W. H. J. Kruit ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Low Dose ◽  
Advanced Breast ◽  
Oral Etoposide ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Dose Oral ◽  
Line Chemotherapy

MONARCH 2: Abemaciclib in combination with fulvestrant in patients with HR+/HER2- advanced breast cancer who progressed on endocrine therapy

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1000-1000 ◽  
Author(s):  
George W. Sledge ◽  
Masakazu Toi ◽  
Patrick Neven ◽  
Joohyuk Sohn ◽  
Kenichi Inoue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Therapy ◽  
Objective Response ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Rank Test ◽  
Clinical Activity ◽  
Phase 3 ◽  
Measurable Disease

1000 Background: Abemaciclib, an oral, selective inhibitor of CDK4 & 6, dosed on a continuous schedule, demonstrated clinical activity as monotherapy in patients (pts) with treatment refractory hormone receptor positive (HR+) metastatic breast cancer (MBC). The tolerability and activity of abemaciclib + fulvestrant (F) supported Phase 3 evaluation. Methods: MONARCH 2 is a double-blind Phase 3 trial of abemaciclib + F vs placebo (P) + F in women with HR+/HER2- advanced breast cancer. Women who progressed on (neo)adjuvant endocrine therapy (ET), ≤12 months from end of adjuvant ET, or on first line ET for MBC and who had not received chemotherapy for metastatic disease were eligible. Pts were randomized 2:1 to receive abemaciclib at 150 mg Q12H (or 200 mg prior to amendment) or P plus F (500 mg, per label) and stratified by metastatic site (visceral, bone only, or other) and resistance to prior ET (primary vs secondary). Pre/perimenopausal pts received a gonadotropin-releasing hormone agonist. The primary objective was investigator-assessed progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and other efficacy and safety endpoints. Assuming a hazard ratio (HR) of 0.703 in favor of abemaciclib + F, 378 events were needed for 90% power at one sided α=.025. Results: 669 pts were randomized to abemaciclib + F (N=446) and to P + F (N=223). 56% of pts had visceral disease, 72% had measurable disease, 25% had primary ET resistance, and 82% were postmenopausal. In the ITT population 379 PFS events were observed with a median PFS of 16.4 m for abemaciclib + F and 9.3 m for P + F (HR: 0.553; 95% CI: 0.449, 0.681, P<.0000001 by log-rank test). In pts with measurable disease, the ORR was 48.1% (3.5% complete response [CR]) for abemaciclib + F and 21.3% (0% CR) for P + F. The most frequent treatment emergent adverse events for abemaciclib + F vs P + F were diarrhea (86.4% vs 24.7%), neutropenia (46.0% vs 4.0%), nausea (45.1% vs 22.9%), and fatigue (39.9% vs 26.9%). Conclusions: Abemaciclib + fulvestrant was an effective treatment in patients with HR+/HER2- advanced breast cancer who progressed on endocrine therapy with significantly improved PFS and ORR. Clinical trial information: NCT02107703.

Mitomycin-C, VP16-213 combination as third line chemotherapy in advanced breast cancer

1982 ◽  
Vol 7 (2-3) ◽  
Author(s):  
G.Perez Manga ◽  
P.L. Madrigal Alonso ◽  
H.Alburquerque Carbuccia
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Mitomycin C ◽  
Advanced Breast ◽  
Third Line ◽  
Line Chemotherapy

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.

High-dose versus low-dose CMFP regimen in advanced breast cancer

1984 ◽  
Vol 25 (4) ◽  
pp. 300-302
Author(s):  
Anand Kumar ◽  
N. N. Khanna ◽  
C. C. Pant ◽  
S. Khanna
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Low Dose ◽  
Advanced Breast ◽  
High Dose

Effective initial therapy of advanced breast cancer with fluorouracil and high-dose, continuous infusion calcium leucovorin.

1992 ◽  
Vol 10 (8) ◽  
pp. 1278-1283 ◽  
Author(s):  
K A Margolin ◽  
J H Doroshow ◽  
S A Akman ◽  
L A Leong ◽  
R J Morgan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Soft Tissue ◽  
Advanced Breast Cancer ◽  
Metastatic Disease ◽  
Advanced Disease ◽  
Objective Response ◽  
Advanced Breast ◽  
High Dose ◽  
Median Response ◽  
Prior Chemotherapy

PURPOSE The use of leucovorin (LV) to modulate fluorouracil (FU)-mediated inhibition of thymidylate synthase has been shown both in vitro and in vivo to improve the antitumor activity of this drug. Based on our previous demonstration that this combination was active in heavily pretreated patients with prior FU exposure, we performed a phase II study of FU and high-dose intravenous calcium LV in patients with advanced breast cancer who had been exposed to no more than one prior chemotherapy regimen. PATIENTS AND METHODS Fifty-one female patients with metastatic breast cancer were entered onto this trial. Patients with metastatic disease limited to soft tissue, lymph nodes, skin, and pulmonary nodules were allowed no prior chemotherapy for advanced disease. Those with metastases in the liver or a lymphangitic pattern on chest x-ray were allowed either a single prior regimen for advanced disease or no therapy for metastatic disease if less than 1 year had elapsed since the completion of adjuvant chemotherapy. FU was given daily for 5 days at 400 mg/m2/d with calcium LV, 500 mg/m2/d, beginning 24 hours before and continuing 12 hours after the first and last FU doses, respectively. RESULTS The overall objective response rate among 45 eligible patients was 36% (95% confidence interval, 22% to 51%). Fourteen of 31 patients in the soft tissue category responded (45%), and two of 14 in the visceral category experienced an objective response (14%). The median response duration was 5 months. Toxicities were moderate leukopenia and mucositis. CONCLUSIONS FU plus LV is an active first-line regimen with antitumor efficacy comparable to that of the anthracyclines, which warrants further exploration in combination with other agents active in advanced breast cancer. FU plus LV in this schedule is also an excellent alternative for patients with medical contraindications to more intensive combination chemotherapy regimens.

scholarly journals Weekly low-dose mitoxantrone plus doxorubicin as second-line chemotherapy for advanced breast cancer

1992 ◽  
Vol 21 (2) ◽  
pp. 133-138 ◽  
Author(s):  
M. Bontenbal ◽  
A. S. Th. Planting ◽  
C. J. Rodenburg ◽  
A. Dees ◽  
J. Verweij ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Low Dose ◽  
Advanced Breast ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Line Chemotherapy
Sign in / Sign up

Export Citation Format

Share Document