RESUMEN
BACKGROUND: Appendiceal neoplasms include tumors ranging from benign-appearing cells with widespread mucin deposits to aggressive poorly differentiated signet ring cell adenocarcinomas. Traditionally, these tumors are treated with cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy. For some patients, cytoreductive surgery is not an option, and minimal published data exist in the management and outcome of these patients. A retrospective analysis was conducted to determine the benefit of modern systemic chemotherapy in patients with disseminated appendiceal neoplasm who were not considered optimal candidates for cytoreductive surgery. METHODS: A retrospective review was conducted using The University of Texas M. D. Anderson Cancer Center tumor registry between January 2000 and July 2005. Response was determined by radiographic response and/or overall clinical benefit. RESULTS: Of 186 patients diagnosed with appendiceal neoplasm, 54 (29%) patients considered to be suboptimal surgical candidates received > or =2 cycles of systemic chemotherapy. Thirty (55.6%) patients had a disease control rate noted as a complete response, partial response, or stable disease. After a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival were determined to be 7.6 months (95% confidence interval [CI], 4-11) and 56 months (95% CI, 36-not applicable), respectively. CONCLUSIONS: Systemic chemotherapy has a role in appendiceal neoplasm patients who are suboptimal candidates for cytoreductive surgery. The intermediate PFS indicates the challenges that exist for appendiceal neoplasm patients in this setting. Prospective randomized trials including systemic chemotherapy are needed to provide further insight into this malignancy, for which no standard exists.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Apéndice/tratamiento farmacológico , Adulto , Anciano , Neoplasias del Apéndice/mortalidad , Neoplasias del Apéndice/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Hipertermia Inducida , Inyecciones Intraperitoneales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Abstract Vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor and has been identified as an important target of cancer therapy. Blocking endothelial cell VEGF activity inhibits tumor angiogenesis; normalizes tumor vasculature, facilitating improved chemotherapy delivery; and prevents the recruitment of progenitor cells from the bone marrow. Bevacizumab, the only United States Food and Drug Administration (FDA)-approved anti-VEGF agent, is a monoclonal antibody that inhibits the binding of VEGF to VEGF receptors. The addition of bevacizumab to standard first- and second-line chemotherapy regimens for the treatment of metastatic colorectal cancer improves overall and progression-free survival times and increases the time to disease progression. Studies are evaluating bevacizumab as adjuvant therapy. The optimal bevacizumab dosage is unknown, but 5 mg/kg every 2 weeks is currently recommended for initial therapy. A surrogate efficacy marker is needed to optimize bevacizumab use, both for dose and patient selection; the clinical applicability of several surrogate efficacy markers is being evaluated. Generally, bevacizumab is well tolerated; however, several serious adverse effects that may occur (e.g., hypertensive crisis) can usually be appropriately prevented or managed. Although current recommendations suggest the administration of the first bevacizumab dose over 90 minutes to prevent infusion-related hypersensitivity reactions, recent study results show that 5 and 10 mg/kg can safely be administered over 10 and 20 minutes, respectively. Whether the addition of bevacizumab to metastatic colorectal cancer treatment regimens is a cost-effective treatment option is unknown; health economic studies are needed. When used for FDA-approved indications or for off-label indications being evaluated in select clinical trials, Medicare reimburses for bevacizumab therapy.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/economía , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/economía , Anticuerpos Monoclonales Humanizados , Antineoplásicos/efectos adversos , Antineoplásicos/economía , Bevacizumab , Ensayos Clínicos como Asunto , Neoplasias Colorrectales/fisiopatología , Análisis Costo-Beneficio , Sistemas de Liberación de Medicamentos , Humanos , Metástasis de la Neoplasia/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
BACKGROUND: Treatment of peritoneal recurrence following surgical resection of intra-abdominal sarcomas presents a significant challenge to clinicians. Historically, treatment with systemic chemotherapy has been ineffective and surgical resection alone has not been durable. We prospectively evaluated the feasibility of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin (CDDP) alone or in combination with mitoxantrone (MITOX) for the treatment of sarcomatosis. METHODS: Two phase I trials of HIPEC were conducted (1998-2003). Eligible patients with evidence of sarcomatosis underwent cytoreductive surgery followed by HIPEC. In the first trial, CDDP dosing was established as 90 mg/m2 with a perfusate time of 90 minutes and temperature of 41 degrees C. In the second trial, MITOX (20 mg/m2) was instilled following perfusion with CDDP. Toxicity, efficacy, and quality of life (QOL) were evaluated. RESULTS: A total of 28 patients were enrolled in the two trials. We noted a higher overall toxicity score and complication rate with combination CDDP/MITOX versus CDDP alone and shorter overall survival duration (5.5 months vs 16.9 months, respectively). In addition, local recurrence rates were similar in both groups (CDDP 79% vs CDDP/MITOX 68%). As expected, QOL scores at 6-8 weeks following HIPEC were 15-25% lower than the baseline scores; however, they returned to baseline at 3-6 months. CONCLUSIONS: Although the HIPEC technique is feasible for patients with sarcomatosis, it is associated with significant toxicity and limited clinical benefit. Combination CDDP/MITOX failed to demonstrate any benefit over CDDP alone; moreover, there was an increase in toxicity.
Asunto(s)
Antineoplásicos/toxicidad , Cisplatino/toxicidad , Hipertermia Inducida , Mitoxantrona/toxicidad , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Sarcoma/tratamiento farmacológico , Sarcoma/cirugía , Adulto , Anciano , Antineoplásicos/administración & dosificación , Quimioterapia del Cáncer por Perfusión Regional/métodos , Cisplatino/administración & dosificación , Ensayos Clínicos Fase I como Asunto , Terapia Combinada , Supervivencia sin Enfermedad , Quimioterapia Combinada , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Neoplasias Peritoneales/mortalidad , Estudios Prospectivos , Calidad de Vida , Sarcoma/mortalidad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: The safety of combined hepatic artery infusion chemotherapy (HAI) and radiofrequency ablation (RFA) for liver metastases has not been assessed. We conducted a study to determine the feasibility of using HAI after RFA for colorectal cancer (CRC) liver metastases. METHODS: Between 1996 and 2001, patients with hepatic metastases from CRC were enrolled onto a prospective study of RFA plus HAI consisting of continuous-infusion floxuridine and bolus fluorouracil. Surgical complications, treatment-related toxicities, and patient outcomes were recorded. RESULTS: Fifty patients were treated with RFA and HAI with or without resection. A median of two lesions per patient, with a median greatest diameter of 2.0 cm, were treated with RFA. Postoperative complications, including 1 death, occurred in 11 of 50 patients. Toxicity from HAI was relatively mild. At 20 months' median follow-up, 32% of patients remained disease free. Ten percent of patients had recurrences at the site of RFA, 30% developed new liver metastases, and 48% developed extrahepatic disease. CONCLUSIONS: RFA of CRC liver metastases followed by HAI is feasible and is associated with acceptable complication and toxicity rates. The high rate of disease recurrence in our patients indicates that novel combinations of regional and systemic therapies are needed to improve patient outcomes.