Multicenter Phase II Study of Capecitabine in Paclitaxel-Refractory Metastatic Breast Cancer

Blum, Joanne L.; Jones, Stephen E.; Buzdar, Aman U.; LoRusso, Patricia; Kuter, Irene; Vogel, Charles L.; Osterwalder, B; Burger, Hans Ulrich; Brown, C.; Griffin, Tom

doi:10.1200/jco.1999.17.2.485

Cited by 731 publications

(435 citation statements)

References 16 publications

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“…Acute radiation toxicities were graded according to the European Organization Therapy Oncology Group (EORTC-RTOG) toxicity criteria. Hand -foot syndrome was graded 1 -3, as defined in previous capecitabine clinical studies (Blum et al, 1999).…”

Section: Study Assessmentsmentioning

confidence: 99%

“…In a preclinical study, capecitabine given orally resulted in consistently higher tissue-to-plasma 5-FU concentration ratios than 5-FU administered intravenously . In addition, capecitabine has also exhibited antitumour activity when given as a monotherapy or in combination with cisplatin in patients with various solid tumours as well as in advanced HNSCC (Blum et al, 1999;Van Cutsem et al, 2001;Kim et al, 2002;Pivot et al, 2003;Park et al, 2004).…”

mentioning

confidence: 99%

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Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

et al. 2005

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We aimed to evaluate the efficacy and safety of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In total, 37 patients with stage III or IV SCCHN were enrolled on the study. The chemotherapy consisted of two cycles of intravenous cisplatin of 80 mg m À2 on day 1 and oral capecitabine 825 mg m À2 twice daily from day 1 to day 14 at 3-week intervals. The radiotherapy (1.8 -2.0 Gy 1 fraction day À1 to a total dose of 70 -70.2 Gy) was delivered to the primary tumour site and neck. The primary tumour sites were as follows: oral cavity (n ¼ 6), oropharynx (n ¼ 11), hypopharynx (n ¼ 8), larynx (n ¼ 3), nasopharynx (n ¼ 6), and paranasal sinus (n ¼ 3). After the chemoradiotherapy, 29 complete responses (78.4%) and 6 partial responses (16.2%) were confirmed. Grade 3 or 4 neutropenia occurred only in two patients, plus grade 3 febrile neutropenia was observed only in one patient. At a median follow-up duration of 19.8 months, the estimated overall survival and progression-free survival rate at 2-year was 76.8 and 57.9%, respectively. Concurrent chemoradiotherapy with capecitabine and cisplatin was found to be well tolerated and effective in patients with locally advanced SCCHN.

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Section: Study Assessmentsmentioning

confidence: 99%

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confidence: 99%

Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

et al. 2005

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“…In the first trial, which included 162 patients (Blum et al, 1999a), the overall response rate was 20% (with a further 43% achieving stable disease) and the median survival was 12.6 months. Additionally, 47% of patients with significant pain at baseline showed a durable reduction in pain scores of at least 50%.…”

Section: Clinicalmentioning

confidence: 99%

“…In a subgroup of 42 patients resistant to both paclitaxel and doxorubicin, the response rate was 29%. In the second study (Blum et al, 1999b), which included 74 patients pretreated with either paclitaxel or docetaxel, the response rate was 25% (27% in patients pretreated with paclitaxel and 20% in patients pretreated with docetaxel). The activity of capecitabine as second-or thirdline therapy thus compares favourably with trials of some other agents reported in the literature.…”

Section: Clinicalmentioning

confidence: 99%

Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

et al. 2002

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Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracyclinepretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 mg m 72 twice daily, days 1 -14, (22 patients)) or a reference arm of i.v. paclitaxel (175 mg m 72 , (20 patients)). Two additional patients were initially randomised to continuous capecitabine 666 mg m 72 twice daily, but this arm was closed following selection of the intermittent schedule for further development. Overall response rate was 36% (95% CI 17 -59%) with capecitabine (including three complete responses) and 26% (95% CI 9 -51%) with paclitaxel (no complete responses). Median time to disease progression was similar in the two treatment groups (3.0 months with capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4 months, respectively). Paclitaxel was associated with more alopecia, peripheral neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse events were diarrhoea, vomiting and hand -foot syndrome. Twenty-three per cent of capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a 510% improvement in Karnofsky Performance Status. Oral capecitabine is active in anthracycline-pretreated advanced/ metastatic breast cancer and has a favourable safety profile. Furthermore, capecitabine provides a convenient, patientorientated therapy.

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“…14,[27][28][29][30] Significant preclinical in vivo activity was also seen in models of breast cancer, pancreatic cancer, and melanoma. [31][32][33][34][35][36][37][38] E7974 thus offers significant promise of activity in taxane-resistant tumor types, regardless of whether the mechanism driving resistance is based on P-glycoprotein or tubulin mutations. 39 In the toxicology studies, E7974 was examined after single intravenous (IV) administration in mice, rats (1, 3, or 6 mg/kg), and dogs (0.1 or 0.23 mg/kg).…”

Section: Introductionmentioning

confidence: 99%

A phase 1 trial of E7974 administered on day 1 of a 21‐day cycle in patients with advanced solid tumors

Rocha-Lima

Bayraktar

MacIntyre

et al. 2012

Cancer

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BACKGROUND: E7974, a synthetic analog of hemiasterlin, interacts with the tubulin molecule and overcomes resistance to other antitubulin drugs (taxanes and vinca alkaloids). METHODS: In a phase 1 study, E7974 was given intravenously over a 2-to 5-minute infusion on day 1 of every 21-day cycle. Adult patients with advanced refractory solid tumors who had adequate organ function and Eastern Cooperative Oncology Group performance status 0 to 2 were eligible for this study. A modified Fibonacci schema was used. The maximal tolerated dose (MTD) was the dose where <2 of 6 patients developed a dose-limiting toxicity (DLT). RESULTS: Twentyeight patients (19 men and 9 women; median age, 64 years) treated at different cohort dose levels (0.18 mg/m 2 , 0.27 mg/m 2 , 0.36 mg/m 2 , 0.45 mg/m 2 , and 0.56 mg/m 2 ) received a total of 66 courses of E7974. The MTD was established at 0.45 mg/m 2 , where 1 of 6 patients experienced DLT (grade 4 febrile neutropenia). Of the 17 refractory colon cancer patients with a median of 3 prior treatments, stable disease was seen in 7 patients (41%). There were no tumor responses. Median progression-free survival was 1.2 months, and median overall survival was 6.7 months. In pharmacokinetic analysis, E7974 was characterized by a fast and moderately large distribution (37.95-147.93 L), slow clearance (2.23-7.15 L/h), and moderate to slow elimination (time to half-life, 10.4-30.5 hours). CONCLUSIONS: This study shows that E7974 once every 21-day cycle shows antitumor activity in patients with refractory solid tumors. The recommended phase 2 dose is 0.45 mg/m 2 .

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Multicenter Phase II Study of Capecitabine in Paclitaxel-Refractory Metastatic Breast Cancer

Abstract: Capecitabine is an active drug in the treatment of paclitaxel-refractory metastatic breast cancer. It has a favorable toxicity profile with the added advantage of being an oral drug administered at home.

Cited by 731 publications

References 16 publications

Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck

Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

A phase 1 trial of E7974 administered on day 1 of a 21‐day cycle in patients with advanced solid tumors

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