A novel capecitabine dosing schedule combined with bevacizumab is safe and active in patients with metastatic breast cancer: A phase II study

Traina, TA; Theodoulou, M.; Dugan, Ute; Feigin, Kimberly N.; Patil, Shekhar; Edwards, Claire; Norton, Lawrence W.; Hudis, C.

doi:10.1200/jco.2008.26.15_suppl.1101

Cited by 6 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have completed a phase I clinical trial in patients with advanced breast cancer supporting this hypothesis[45]. Based on additional preclinical support, phase II studies of capecitabine 7 - 7 in combination with biological agents are ongoing[46, 47]. Furthermore, a prospective, randomized, phase III trial of the comparative efficacy and toxicity of the novel schedule versus the conventional schedule is planned through the SLACOM cooperative group.…”

Section: Discussionmentioning

confidence: 99%

Optimizing Chemotherapy Dose and Schedule by Norton-Simon Mathematical Modeling

Traina

Dugan

Higgins

et al. 2010

View full text Add to dashboard Cite

Background To hasten and improve anticancer drug development, we created a novel approach to generating and analyzing preclinical dose-scheduling data so as to optimize benefit-to-toxicity ratios. Methods We applied mathematical methods based upon Norton-Simon growth kinetic modeling to tumor-volume data from breast cancer xenografts treated with capecitabine (Xeloda®, Roche) at the conventional schedule of 14 days of treatment followed by a 7-day rest (14 - 7). Results The model predicted that 7 days of treatment followed by a 7-day rest (7 - 7) would be superior. Subsequent preclinical studies demonstrated that this biweekly capecitabine schedule allowed for safe delivery of higher daily doses, improved tumor response, and prolonged animal survival. Conclusions We demonstrated that the application of Norton-Simon modeling to the design and analysis of preclinical data predicts an improved capecitabine dosing schedule in xenograft models. This method warrants further investigation and application in clinical drug development.

show abstract

Section: Discussionmentioning

confidence: 99%

Optimizing Chemotherapy Dose and Schedule by Norton-Simon Mathematical Modeling

Traina

Dugan

Higgins

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Moreover, the 7/7 regimen may simplify administration when capecitabine is delivered with agents administered 2 or 3 weeks. Preliminary results from a Phase II study evaluating a 7/7 dosing schedule with capecitabine 2000 mg/m 2 twice a day in combination with bevacizumab (10 mg/kg every 2 weeks) appear to reinforce the available preclinical and clinical evidence that the capecitabine 7/7 dosage schedule is clinically active and well tolerated, and may provide the greatest acceptable doseintensity and dose-density [46]. It should be emphasized that the 7/7 schedule is supported by Phase I and preliminary Phase II data, and further research is necessary.…”

Section: Dosing and Safetymentioning

confidence: 76%

Capecitabine: treatment options in metastatic breast cancer

Kaklamani¹,

Gradishar

2009

Expert Review of Obstetrics & Gynecology

View full text Add to dashboard Cite

The most recent epidemiological estimates indicate that 182,400 women in the USA were diagnosed with breast cancer in 2008 [101]. While the majority of cases are diagnosed at the localized stage, 31% will develop metastatic breast cancer [101]. The introduction of new therapeutic regimens, including novel chemotherapeutic and biologic agents, represents a significant advance in the treatment of breast cancer. Breast cancer incidence rates have decreased by 3.1% from 2001 to 2005 [101], a reduction that is attributed, in part, to a substantial reduction in the use of hormone-replacement therapy [1][2][3]. Nevertheless, while incidence rates for localized breast cancer have declined, metastatic breast cancer rates have remained stable [102]. Since metastatic breast cancer remains essentially incurable, the goals of treatment are largely palliative, focused on managing quality of life, delaying disease progression and prolonging overall survival (OS) time.The heterogeneity of metastatic breast cancer underscores the need to take into account tumor characteristics and the patient's needs when determining a treatment strategy. Chemotherapy is recommended when a rapid response is necessary and when the disease is hormone receptor-negative, or endocrine-unresponsive. In patients with hormone receptorpositive breast cancer, endocrine therapy may be utilized. Prognostic factors for survival in patients with metastatic breast cancer include hormone receptor status, disease aggressiveness, responsiveness to previous therapy (if any), time to recurrence/development of metastatic breast cancer after primary diagnosis, site of metastases and number of metastatic sites. One challenge in therapy with cytotoxic agents is to provide sustained exposure of malignant cells to therapeutic drug concentrations without compromising patient comfort and safety.Capecitabine (Xeloda ® , Hoffman-LaRoche, Basel, Switzerland) is widely used in the treatment of metastatic breast cancer. As an oral agent, capecitabine is devoid of the complications associated with intravenous infusions, such as thrombosis, bleeding and infection. In combination with docetaxel, capecitabine has been shown to extend survival in patients with metastatic breast cancer and may be suited to patients with rapidly progressing disease [4]. In this article, we review the pharmacology and clinical efficacy and safety data for capecitabine in the treatment of metastatic Capecitabine (Xeloda ® ) is an orally administered chemotherapeutic agent, widely used for metastatic breast cancer treatment. Preclinical and clinical studies demonstrate selective enzymatic conversion of capecitabine into 5-fluorouracil, a potent cytotoxic agent within malignant tumors. Capecitabine is the only cytotoxic agent without cumulative toxicity and it exhibits synergistic activity when used in combination with a wide range of other cytotoxic and biologic agents. Capecitabine monotherapy results in an objective response rate of 15-37% in patients with metastatic breast cancer in the adjuvant settin...

show abstract

Individualizing the Approach to the Older Woman with Triple-Negative Breast Cancer

Singh

Lichtman

2017

Triple-Negative Breast Cancer

View full text Add to dashboard Cite

A novel capecitabine dosing schedule combined with bevacizumab is safe and active in patients with metastatic breast cancer: A phase II study

Cited by 6 publications

References 0 publications

Optimizing Chemotherapy Dose and Schedule by Norton-Simon Mathematical Modeling

Optimizing Chemotherapy Dose and Schedule by Norton-Simon Mathematical Modeling

Capecitabine: treatment options in metastatic breast cancer

Individualizing the Approach to the Older Woman with Triple-Negative Breast Cancer

Contact Info

Product

Resources

About