scholarly journals Fixed-dose capecitabine is feasible: results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer

2013 ◽  
Vol 139 (1) ◽  
pp. 135-143 ◽  
Author(s):  
Michelle A. Rudek ◽  
Roisin M. Connolly ◽  
Janelle M. Hoskins ◽  
Elizabeth Garrett-Mayer ◽  
Stacie C. Jeter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Fixed Dose ◽  
Pharmacogenetic Study

Subcutaneous Trastuzumab with Pertuzumab and Docetaxel in HER2-Positive Metastatic Breast Cancer: Final Analysis of MetaPHER, A Phase 3b Single-Arm Safety Study

2020 ◽  
Author(s):  
Sherko Kümmel ◽  
Carlo Alberto Tondini ◽  
Jacinta Abraham ◽  
Zbigniew Nowecki ◽  
Bartosz Itrych ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Fixed Dose ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

Abstract BACKGROUND Intravenous trastuzumab, pertuzumab, and docetaxel is first-line standard of care for patients with HER2-positive metastatic breast cancer. Subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy has shown similar safety and tolerability to intravenous trastuzumab in patients with HER2-positive early and metastatic breast cancer; however, in the metastatic setting, this has yet to be shown globally.METHODS In this open-label, single-arm, multicenter phase 3b study, eligible patients were ≥18 years old with histologically/cytologically confirmed previously untreated HER2-positive metastatic breast cancer. All patients received ≥1 dose of subcutaneous trastuzumab (fixed-dose 600 mg) plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance dose: 420 mg/kg) and docetaxel (≥6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy.RESULTS At clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia. The most common grade ≥3 adverse events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%.CONCLUSIONS Efficacy/safety results of subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in metastatic breast cancer are consistent with historical evidence of intravenous trastuzumab. These findings further support the body of evidence indicating that subcutaneous administration does not affect the safety and efficacy profile of trastuzumab in HER2-positive breast cancer. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02402712 (date of registration: 30th March 2015)

A phase II pharmacokinetic/pharmacogenetic (PK/PG) study using fixed-dose capecitabine in metastatic breast cancer (MBC).

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 1067-1067
Author(s):  
R. M. Connolly ◽  
M. A. Rudek ◽  
H. L. Mc Leod ◽  
E. Garrett-Mayer ◽  
S. C. Jeter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Metastatic Breast ◽  
Fixed Dose

Mitoxantrone dose augmentation utilizing filgrastim support in combination with fixed-dose 5-fluorouracil and leucovorin in women with metastatic breast cancer

1997 ◽  
Vol 43 (3) ◽  
pp. 193-200 ◽  
Author(s):  
James N. Ingle ◽  
Carl G. Kardinal ◽  
Vera J. Suman ◽  
Michael H. Veeder ◽  
Paul L. Schaefer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Fixed Dose

scholarly journals Subcutaneous trastuzumab with pertuzumab and docetaxel in HER2-positive metastatic breast cancer: Final analysis of MetaPHER, a phase IIIb single-arm safety study

2021 ◽  
Author(s):  
Sherko Kuemmel ◽  
Carlo A. Tondini ◽  
Jacinta Abraham ◽  
Zbigniew Nowecki ◽  
Bartosz Itrych ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Subcutaneous Administration ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Fixed Dose ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

Abstract Purpose Intravenous trastuzumab, pertuzumab, and docetaxel are first-line standard of care for patients with HER2-positive metastatic breast cancer (mBC). MetaPHER is the first study assessing the safety and tolerability of subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy in a global patient population with HER2-positive mBC. Methods In this open-label, single-arm, multicenter, phase 3b study, eligible patients were ≥ 18 years old with histologically/cytologically confirmed previously untreated HER2-positive mBC. All received ≥ 1 subcutaneous trastuzumab 600 mg fixed dose plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance: 420 mg/kg) and docetaxel (≥ 6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy. Results At clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia; the most common grade ≥ 3 events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%. Conclusions Safety and efficacy with subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in mBC are consistent with historical evidence of intravenous trastuzumab with this combination. Findings further support subcutaneous administration not affecting safety/efficacy profiles of trastuzumab in HER2-positive BC with increased flexibility in patient care. A fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection has recently been approved for the treatment of HER2-positive early/mBC, further addressing the increasing relevance of and need for patient-centric treatment strategies. Trial registration NCT02402712

scholarly journals Efficacy and Safety of the All-Oral Schedule of Metronomic Vinorelbine and Capecitabine in Locally Advanced or Metastatic Breast Cancer Patients: The Phase I-II VICTOR-1 Study

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
M. E. Cazzaniga ◽  
V. Torri ◽  
F. Villa ◽  
N. Giuntini ◽  
F. Riva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Phase Ii ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Fixed Dose ◽  
Toxicity Profile ◽  
Breast Cancer Patients

Background. Vinorelbine (VRB) and capecitabine (CAPE) are demonstrated to be active in pretreated metastatic breast cancer patients. Different studies have demonstrated that the metronomic treatment is active with an acceptable toxicity profile. We designed a Phases I-II study to define the MTD of oral metronomic, VRB, and CAPE.Patients and Methods. Phase I: fixed dose of CAPE was 500 mg thrice a day, continuously. Level I of VRB was 20 mg/tot thrice a week for 3 weeks (1 cycle). Subsequent levels were 30 mg/tot and 40 mg/tot (Level III), respectively, if no Grades 3-4 toxicity were observed in the previous level. Phase II: further 32 patients received the MTD of VRB plus CAPE for a total of 187 cycles to confirm toxicity profile.Results. 12 patients were enrolled in Phase I and 22 in Phase II. Phase I: the MTD of VRB was 40 mg. Phase II: 187 cycles were delivered, observing 5.9% of Grades 3-4 toxicity. 31 patients are evaluable for efficacy, obtaining a clinical benefit rate of 58.1%.Conclusion. MTD of VRB with fixed dose of CAPE was 40 mg thrice a week and was the recommended dose for the ongoing Phase II multicenter study.

Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study.

1995 ◽  
Vol 13 (11) ◽  
pp. 2688-2699 ◽  
Author(s):  
L Gianni ◽  
E Munzone ◽  
G Capri ◽  
F Fulfaro ◽  
E Tarenzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Antitumor Efficacy ◽  
Severe Neutropenia ◽  
Fixed Dose ◽  
Median Response

PURPOSE To define the maximum-tolerated dose (MTD) and better tolerated sequence of paclitaxel by 3-hour infusion plus bolus doxorubicin (DOX) and to evaluate antitumor efficacy. PATIENTS AND METHODS Thirty-five women with metastatic breast cancer (dominant visceral metastases in 56%, and involvement of > or = three sites in 67%) who never received chemotherapy of any type were studied. Paclitaxel every 3 weeks (125 mg/m2 starting dose) was increased by 25-mg/m2 steps in subsequent cohorts of patients. DOX (60 mg/m2 fixed dose) was administered 15 minutes before the start of or after the end of paclitaxel for a maximum of eight cycles. Subsequently, patients in continuous response could receive single-agent paclitaxel (175 to 200 mg/m2 every 3 weeks). The drug sequence was alternated in consecutive patients and in the first two cycles. RESULTS Severe neutropenia that lasted greater than 7 days (n = 4), febrile neutropenia (n = 7) and grade III oral mucositis (n = 6) defined the MTD of paclitaxel at 200 mg/m2 in 34 assessable patients. Grade II peripheral neuropathy occurred in 33% of patients. Six women (18%) developed clinically reversible congestive heart failure (CHF) after a median of 480 mg/m2 total DOX. Drug sequence had no effect on toxicities. High efficacy on all metastatic sites in 32 assessable patients accounted for a 41% complete response (CR) rate (95% confidence interval [CI], 24% to 59%) and 94% overall-response rate (95% CI, 79% to 99%). After a median follow-up of 12 months (range 3 to 18), the median response duration is 8 months (range, 2+ to 18+) for complete responders and 11 months (range 1+ to 15+) for partial responders. CONCLUSION The rate of CR and incidence of CHF may be an expression of therapeutic and toxic enhancement due to the schedule used in this trial. Until clarification of this possibility, this promising combination should be used in investigational trials.

Results of first-line weekly paclitaxel (P) + gemcitabine (G) in metastatic breast cancer (MBC): An AERO phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1103-1103
Author(s):  
M. Mousseau ◽  
D. Serin ◽  
T. Petit ◽  
F. Priou ◽  
L. Zelek
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Metastatic Breast ◽  
Weekly Paclitaxel ◽  
Fixed Dose ◽  
Weekly Schedule ◽  
Efficient Treatment ◽  
Metastatic Sites

1103 Background: Three weekly paclitaxel and gemcitabine (PG) combination is recognised as an efficient treatment of metastatic breast cancer. Weekly paclitaxel has shown improved results comparatively with the three weekly administration. We conducted a study to evaluate a weekly schedule of PG combination in fist line treatment of metastatic breast cancer (MBC). Patients and methods: Patients with MBC were enrolled in this study to evaluate the feasibility and efficacy of P 80mg/m2 D1, 8, 15 and G 1,250 mg/m2 D1, 8 (at fixed dose rate of 10mg/m2 /min) and cycles were repeated every 21 days. This phase II trial had a 2 stages design. Overall response rate was the primary end point. Results: In the first step of the trial 19 pts were enrolled with a median age of 59.5 (range 40 - 74). Baseline ECOG < 2 in 89% of pts. Main metastatic sites were: bone (36 %), lung (36%), liver (36%) and lymph nodes (32%). 52 % of pts had only one metastatic site. Previous treatments included surgery (89%), radiotherapy (73%), anthracycline based chemotherapy (74%) and adjuvant hormontherapy (52%). 18 pts were evaluable for efficacy and toxicity. 6 achieved PR, 5 SD and 6 PD resulting in an ORR of 33%. All patients were evaluable for toxicity. Main grade 3–4 toxicities per patient were neutropenia (67%), febrile neutropenia (5%), anemia (17%), thrombocytopenia (33%), trasnsaminases leveations (11%) and dyspnia (5%). Chemotherapy was delayed frequently for toxicity reasons (delays or arrest for toxicity in 15 pts). Conclusion: This weekly PG regimen has some activity in MBC. Although life-threatening toxicities were uncommon, delays in haematological recovery are frequent, making the investigated schedule unsuitable for further studies. [Table: see text]

Fixed dose, dose-dense capecitabine in metastatic breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12593-e12593
Author(s):  
Anne O'Dea ◽  
Meshaal Khan ◽  
Haley Isabela Haines ◽  
Bruce F. Kimler ◽  
Lauren Elizabeth Nye ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Dose Reduction ◽  
De Novo ◽  
Standard Dose ◽  
Metastatic Breast ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Optimal Dose ◽  
Fixed Dose

e12593 Background: Capecitabine (C) is the only oral chemotherapy agent for metastatic breast cancer (MBC), and compared to IV agents, can be continued indefinitely if toxicities can be managed. The optimal dose and schedule of C are not known. FDA approved dose of 2500 mg/m2 daily is associated with median PFS (progression free survival) of 4-5 months and dose reduction and discontinuation rates from toxicity of 35% and 16% respectively. According to Norton-Simon mathematical model of tumor growth in which dosing schedules are determined based on efficacy, a 7 day on and 7 days off (7-7) schedule of C was predicted as optimal. We report efficacy and toxicity of fixed dose C (1500 mg BID) on a 7-7 schedule in MBC. Methods: Retrospective chart review of patients with MBC treated at our institution between June 2013 and December 2018 and received fixed dose C (1500 mg BID) on a 7-7 dosing schedule were included. Results: 39 patients with MBC were identified; 14 (35%) had de novo MBC and 25 (62.5%) had recurrent disease. 31 (77.5%) had ER+ disease, 6 (15%) were HER2+, and8 (20.5%) had triple negative breast cancer (TNBC). 10 (25%) had received no prior chemotherapy, 15 (37.5%) had received 1 line of chemotherapy, and 14 (35%) had received ≥2 lines of chemotherapy. Median PFS was 13 months. PFS was 17 months in ER+ patients and 8 months in patients with TNBC. Palmar plantar erythrodysesthesia (PPE) was the most frequent toxicity with 11 (27.5%) having mild PPE, 2 (5%) with moderate PPE, and 5 (12.5%) with severe PPE. Mild diarrhea was experienced by 14 (35%) and one patient experienced severe diarrhea. One patient experienced grade 3 neutropenia. No patients discontinued C due to toxicity. 11 (27.5%) required a dose reduction. Conclusions: Fixed dose capecitabine (1500 mg oral BID) on a 7 day on and 7 day off schedule is associated with encouraging PFS and has limited toxicity and a low rate of dose reduction and therapy discontinuation. Randomized trial comparing this dose and schedule of capecitabine to standard dose and schedule of capecitabine is ongoing.

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