Phase II evaluation of capecitabine in refractory nonsquamous cell carcinoma of the cervix: a Gynecologic Oncology Group study.
ABSTRACT We conducted a multi-institutional study to assess the activity and toxicity of capecitabine in patients with persistent or recurrent nonsquamous cancer of the cervix. Eligible patients were required to possess adequate renal, hepatic and bone marrow function and a Gynecologic Oncology Group performance status of 0-2. Histologic confirmation of the original primary cancer was mandated. Patients must have received one prior systemic chemotherapeutic regimen for cervical cancer that did not include the chemotherapy that may have been administered in conjunction with prior radiation therapy. The initial dose schedule was 2500 mg/m2 orally daily in two divided doses for 14 consecutive days, followed by a 7-day rest, such that each cycle was 21 days. Responses were assessed using response evaluation criteria in solid tumors. Twenty-one patients were entered into the trial. One patient was declared ineligible for wrong cell type; thus, 20 were evaluable for toxicity. A median of 2.5 cycles was administered (range 1-11). There was one septic death. Grade 4 neutropenia, renal, neurologic, and pulmonary toxicity was seen in 5%, 5%, 5%, and 10% patients, respectively. There were no responses. Nine patients (45%) each had stable disease and nine showed progression. The remaining two cases (10%) did not have subsequent disease assessment and response could not be assessed. Oral capecitabine at the dose and schedule tested has insignificant activity in nonsquamous cervical cancer patients previously treated with chemotherapy.
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ABSTRACT: Capecitabine is active against anthracycline- and taxane-pretreated metastatic breast cancer. Post-marketing use of capecitabine at the FDA-approved dose (2500 mg/m2/day) leads to unacceptable toxicity in many patients. Dose reductions anecdotally improve tolerability without compromising efficacy. This retrospective analysis was designed to verify these anecdotal reports. Patients and methods: We retrospectively reviewed the records of 141 consecutive patients with metastatic breast cancer identified from pharmacy records as receiving capecitabine outside of a clinical trial between May 1998 and February 1999. Responses were defined as clinical improvement (ID), stabilization of disease (SD) for 6 weeks or longer, or progression (PD). Patients were grouped according to the starting dose level of capecitabine: A=2500+/-5% (dose range 2385-2560) mg/m2/day; B=2250+/-5% (range 2130-2350) mg/m2/day; C < or = 2000+5% (range 1000-2100) mg/m2/day. We also reviewed the safety profile of capecitabine at these doses and performed a safety review of capecitabine in phase II and III metastatic breast and colorectal cancer trials. Clinical data were available for 113 patients (105 for response, 106 for toxicity). The median age was 52.5 years and the mean number of prior metastatic chemotherapy regimens was 2 (range 0-7). The mean capecitabine starting dose was 2220 mg/m2/day and the median number of cycles administered was 4 (range 1-19). The mean tolerated dose was 2040 mg/m2/day (range 960-2670). Grade 3/4 toxic effects at dose levels A, B and C, respectively, included palmar-plantar erythrodysesthesia (33%, 63%, 20%), diarrhea (13%, 12%, 3%), stomatitis (8%, 0%, 3%), and nausea/vomiting (4%, 6%, 5%). Forty per cent of all patients required capecitabine dose reductions; fewer patients treated with 2000 mg/m2/day required dose modification (28%). Five per cent of the patients required discontinuation of capecitabine owing to toxicity. Patients started at the lowest doses of capecitabine did not have poorer response rates or shorter time to progression. This retrospective analysis supports a starting dose of 2000 mg/m2/day because of its superior therapeutic index; however, patients may still have toxic effects and individualization of dosing is necessary. A phase III, multicenter, randomized study to establish the safety and efficacy of different doses of capecitabine is urgently needed.Annals of Oncology 09/2005; 16(8):1289-96. · 7.38 Impact Factor
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ABSTRACT: Anticancer cytotoxic agents go through a process by which their antitumor activity-on the basis of the amount of tumor shrinkage they could generate-has been investigated. In the late 1970s, the International Union Against Cancer and the World Health Organization introduced specific criteria for the codification of tumor response evaluation. In 1994, several organizations involved in clinical research combined forces to tackle the review of these criteria on the basis of the experience and knowledge acquired since then. After several years of intensive discussions, a new set of guidelines is ready that will supersede the former criteria. In parallel to this initiative, one of the participating groups developed a model by which response rates could be derived from unidimensional measurement of tumor lesions instead of the usual bidimensional approach. This new concept has been largely validated by the Response Evaluation Criteria in Solid Tumors Group and integrated into the present guidelines. This special article also provides some philosophic background to clarify the various purposes of response evaluation. It proposes a model by which a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment. Methods of assessing tumor lesions are better codified, briefly within the guidelines and in more detail in Appendix I. All other aspects of response evaluation have been discussed, reviewed, and amended whenever appropriate.JNCI Journal of the National Cancer Institute 03/2000; 92(3):205-16. · 14.34 Impact Factor
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ABSTRACT: The aim of this study was to investigate the changes in two of the enzymes involved in fluorouracil metabolism, thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD), in uterine cervical squamous cell cancer tissue after radiotherapy. Cervical tissue from 27 patients diagnosed with stage IIIB or IV uterine cervical squamous cell cancer was compared with normal cervical tissue from 33 patients with benign gynecologic diseases. Expression of TP and DPD in the cervical tissues was measured using enzyme-linked immunosorbent assays. TP and DPD expression before and after irradiation with 10 and 20 Gy was measured in 9 of the 27 patients with cervical cancer. Before irradiation, DPD expression in cancer tissue did not differ from that in normal tissue. TP expression and the TP/DPD ratio were significantly higher in cancer tissue than in normal tissue ( P<0.00001). TP and DPD expression and the TP/DPD ratio were not significantly changed by irradiation with 10 and 20 Gy. TP expression and the TP/DPD ratio after irradiation with 10 and 20 Gy were significantly higher than in normal tissue. The increased TP expression and the elevated TP/DPD ratio following irradiation with up to 20 Gy may offer an increased clinical advantage to chemoradiotherapy with capecitabine or doxyfluridine over radiotherapy alone.Cancer Chemotherapy and Pharmacology 02/2004; 53(2):151-4. · 2.80 Impact Factor