scholarly journals Gefitinib in Combination with Weekly Docetaxel in Patients with Metastatic Breast Cancer Caused Unexpected Toxicity: Results from a Randomized Phase II Clinical Trial

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Olav Engebraaten ◽  
Hege Edvardsen ◽  
Erik Løkkevik ◽  
Bjørn Naume ◽  
Vessela Kristensen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Partial Response ◽  
Cancer Patients ◽  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitor ◽  
Metastatic Breast ◽  
Treatment Modalities ◽  
Breast Cancer Patients

In patients with metastatic breast cancer, taxane treatment demonstrates activity but is not curative. Targeted treatment modalities are therefore necessary in order to improve outcomes in this group. A randomized placebo-controlled phase II trial was initiated to evaluate effect and toxicity of gefitinib (250 mg QD) and docetaxel 35 mg/m2 (six of seven weeks) (NCT 00319618). The inclusion of 66 patients was planned. The study was closed due to treatment-related toxicity. Of the 18 included patients, seven (of which three received gefitinib) were withdrawn from the study due to toxicity. Of the nine patients receiving gefitinib and chemotherapy, one achieved a partial response and four stable disease. In the chemotherapy of nine patients, four had a partial response and four stable disease. The breast cancer patients in this study were genotyped using a panel of 14 single-nucleotide polymorphisms (SNPs), previously found associated with docetaxel clearance in a cohort of lung cancer patients. We were unable to identify genes related to toxicity in this study. Nevertheless, toxicity was aggravated by the addition of the tyrosine kinase inhibitor. In conclusion, despite adequately tolerated as monotherapy, combination regimens should be carefully considered for overlapping adverse events in order to avoid increased treatment-related toxicity.

Weekly Paclitaxel in Metastatic Breast Cancer Patients: A Phase II Study

2002 ◽  
Vol 88 (6) ◽  
pp. 470-473 ◽  
Author(s):  
Stefania Gori ◽  
Anna Maria Mosconi ◽  
Carlo Basurto ◽  
Roberta Cherubini ◽  
Verena De Angelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Cancer Patients ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Grade 3

Aims and background Paclitaxel, a microtubule inhibitor, is one of the most active drugs in metastatic breast cancer. A weekly schedule, at a median dose-intensity of 91 mg/m2, is effective and has less side effects than a 3-week schedule. In this phase II study, we evaluated the toxicity and the activity of weekly 1 hr paclitaxel infusions in metastatic breast cancer patients. Study design Between February 1999 and February 2001, 26 patients with metastatic breast cancer were treated with weekly paclitaxel (60–90 mg/m2/1 hour iv infusion/weekly). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, paclitaxel was stopped after 6 months of therapy. Results At a median follow-up of 18.7 months (range, 6.8–30.8), all patients are assessable for response and toxicity. We obtained 8 partial responses (30.8%), 8 stable disease (30.8%) and 10 disease progression (38.4.%). The overall response was 30.8% (95% CI, 13.1–48.5). The median duration of response was 7.6 months (range, 1.8–12.4); median time to progression was 4.86 months (range, 1.4–12.4); median overall survival was 9.9 months (range, 1.7–29.2+). Treatment was well tolerated. Hematological toxicity was mild and only one patient developed grade 3 anemia. Two patients experienced grade 3 cardiovascular toxicity; both had received anthracycline-based regimens. Conclusions In our experience, weekly administration of paclitaxel shows a substantial degree of activity even in pretreated metastatic breast cancer patients. The toxicity profile is favorable.

Safety and Efficacy of Using a Single Agent or a Phase II Agent Before Instituting Standard Combination Chemotherapy in Previously Untreated Metastatic Breast Cancer Patients: Report of a Randomized Study—Cancer and Leukemia Group B 8642

1999 ◽  
Vol 17 (5) ◽  
pp. 1397-1397 ◽  
Author(s):  
Mary E. Costanza ◽  
Raymond B. Weiss ◽  
I. Craig Henderson ◽  
Larry Norton ◽  
Donald A. Berry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Single Agent ◽  
Metastatic Breast ◽  
Response Rates ◽  
Breast Cancer Patients ◽  
Safety And Efficacy

PURPOSE: We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF. RESULTS: The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = .24). However, in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P = .078). Although survival and response duration also were not statistically significantly different between the two study arms (P = .074 and P = .069, respectively), there was a suggestion of benefit for the CAF-only arm. CONCLUSION: The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer.

scholarly journals Phase II Study of Celecoxib and Trastuzumab in Metastatic Breast Cancer Patients Who Have Progressed after Prior Trastuzumab-Based Treatments

2004 ◽  
Vol 10 (12) ◽  
pp. 4062-4067 ◽  
Author(s):  
Chau T. Dang ◽  
Andrew J. Dannenberg ◽  
Kotha Subbaramaiah ◽  
Maura N. Dickler ◽  
Mark M. Moasser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Breast Cancer Patients
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