A multi-center phase II study of oxaliplatin, irinotecan, and capecitabine in advanced gastric/gastroesophageal junction carcinoma
Developmental Therapeutics Program, Case Comprehensive Cancer Center, Cleveland, OH, USA. Cancer Chemotherapy and Pharmacology
(Impact Factor: 2.77).
09/2008; 63(5):851-7. DOI: 10.1007/s00280-008-0807-6
There is no standard first-line therapy for advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma and the prognosis remains poor. Our institution conducted a phase I study of oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule. The regimen was tolerated; pharmacodynamic studies revealed no drug interactions, and there was one confirmed response in a gastric cancer patient. We performed a phase II trial in advanced gastric and GEJ adenocarcinoma to determine response rate and response duration.
This was a multi-center single treatment arm study involving six sites. Only prior adjuvant therapy was allowed. Patients had ECOG performance status of 0-2, adequate organ function, and were able to tolerate oral medications. All patients received oxaliplatin 60 mg/m(2) intravenously (IV) and irinotecan 50 mg/m(2) IV weekly times 4 weeks with a 2-week rest period. Capecitabine 450 mg bid orally was received on days 1 through 5 every week for 4 weeks, followed by a 2-week rest. Patients were assessed for response after the first two cycles; response duration, overall survival, and adverse events were also recorded. We estimated an improvement in historical response rate by 30% would have clinical meaning.
A total of 39 patients were accrued and all were assessed for toxicity; 30 patients were evaluable for response. The median age was 57.8 years (31-79 years) and 74% were male. Two patients had a complete response, with nine patients achieving a partial response. The total response rate was 28%, with nine patients not evaluable for response. The median response duration was noted at 5.97 months and median overall survival was 8.98 months. There were no grade 5 treatment related events, with all deaths secondary to disease progression. Only five grade 4 events occurred (neutropenia, hyperkalemia, hypokalemia (2), thrombosis/embolism) without grade 4 diarrhea or sensory neuropathy.
Oxaliplatin, irinotecan, and capecitabine given in a novel, weekly schedule does induce responses in advanced gastric and GEJ adenocarcinoma. However, the total response rate is modest and not an improvement over other regimens.
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ABSTRACT: MEDICATION SAFETY Overlooked Renal Dosage Adjustments A retrospective analysis of 647 patients at hospital discharge com-pared required renal dosage adjust-ments to dosage actually prescribed. This study was conducted at VieCuri Medical Centre in Venlo, Netherlands. Patient demographics and renal function data were col-lected, and dosage adjustment needs were assessed via the pharmacy-supported discharge counseling ser-vice. The incidence of inappropriate dosing based on renal function was measured at hospital discharge. Thirty-seven percent of patients evaluated during the study period (237/647) had a creatinine clear-ance less than 51 mL/min/1.73 m 2 ; dosage adjustment was warranted in 23.9% (411/1,718) of prescrip-tions. When dosage adjustment should have been performed, more than 40% of prescriptions (169/411; 41.1%) were inappropri-ate for renal function (9.8% of pre-scriptions overall; 169/1,718). Fur-thermore, 60.4% (102/169) of inappropriate prescriptions pos-sessed the potential for moderate or severe clinical consequences, as evaluated by a panel of two clinical pharmacologists and one nephrolo-gist. Study authors also noted a lack of standardized dosing guidelines for agents requiring renal dosage adjustment. The authors also sug-gested that augmenting medication systems by adding dynamic renal dosing alerts would improve moni-toring. Summary: A comparison of suggested renal dosing and actual dosing at hospital discharge revealed that appropriate prescribing may be overlooked. van Dijk EA, Drabbe NRG, Kruijtbosch M, De Smet PAGM. Drug dosage adjust-ments according to renal function at hos-pital discharge. Ann Pharmacother. 2006;40:1254-1260.
Hospital pharmacy 12/1122; 41(7). DOI:10.1310/hpj4311-937
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ABSTRACT: Small cell cancers of the gastrointestinal tract are part of a family of extrapulmonary small cell carcinomas. These tumors can occur anywhere in the body and generally carry a poor prognosis. Treatment usually consists of a combination of chemotherapy and radiation therapy. We present two cases illustrating diagnostic and treatment issues and review the literature on the treatment of this uncommon but aggressive family of tumors.
Tumori 09/2010; 96(5):780-3. · 1.27 Impact Factor
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ABSTRACT: In the United States, poor patient tolerability of the standard capecitabine dosing regimen (1250 mg/m2 twice daily on days 1-14 administered every 21 days) limits the established benefit of the agent. The observation that patient tolerability improves and efficacy is maintained with lower doses led to the investigation of various doses and schedules in patients with metastatic breast cancer. Capecitabine monotherapy in daily doses of 1000-2560 mg/m2 or in combination with a taxane in daily doses of 825-1250 mg/m2 has confirmed that tolerability improves and efficacy is maintained with lower-than-standard doses. Similar results have been observed with various dosing schedules, including continuous administration and 28-day, 7-day, and 7-days-on/7-days-off cycles. These findings suggest that capecitabine administered in a variety of doses and schedules might be a viable alternative to anthracycline-containing regimens as first- or second-line treatment in patients with metastatic breast cancer.
Clinical Breast Cancer 03/2010; 10(2):130-5. DOI:10.3816/CBC.2010.n.017 · 2.11 Impact Factor
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