Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer.

BACKGROUND: The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study. PATIENTS AND METHODS: Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled. RESULTS: A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6 months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) for WT KRAS mCRC was 23.9 months (95% CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P = 0.17 (68% OS events). An exploratory analysis of updated survival (>80% OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95% CI 0.70-0.98; P = 0.03 for WT KRAS mCRC. The adverse event profile was consistent with the primary analysis. CONCLUSIONS: In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.

Combined intensive chemoradiotherapy for organ preservation in patients with resectable and non-resectable oesophageal cancer.

From January 1990 to April 1993, 60 oesophageal cancer patients were enrolled in a protocol of non-surgical treatment that consisted of induction chemotherapy followed by concurrent chemoradiotherapy. Induction chemotherapy consisted of cisplatin 40 mg/m2 intravenous bolus days 1, 2, 14, 15; 24 h continuous infusion of 5-fluorouracil (5-FU) 1000 mg/m2 days 1 and 14; leucovorin 20 mg/m2 days 1 and 14 given before and with 5-FU; bleomycin 30 UI days 1 and 14; mitomycin C 10 mg/m2 day 14. Concurrent chemoradiotherapy consisted of 60 Gy (6 weeks) from day 21 and cisplatin 70 mg/m2 days 28, 42 and 56; leucovorin 20 mg/m2 followed by 5-FU 425 mg/m2 days 28, 35, 42, 49 and 56. Complete response occurred in 44 of 55 evaluable patients (80%). The median survival is 32 months; the actuarial survival at 40 months is 35% (CI 18-53). These results appear improved over those reported with surgery or radiation alone, and suggest that organ preservation as a secondary treatment goal should be vigorously investigated.

Treatment of pain and other symptoms in cancer patients: patterns in a North American and a South American hospital.

The charts of 200 consecutive patients with cancer pain admitted to a major teaching hospital in Edmonton, Canada (n = 100) and in Buenos Aires, Argentina (n = 100) were reviewed to assess the differences between North American (NA) and South American (SA) facilities in patterns of treatment of pain and other symptoms. Criteria for eligibility and methods were identical in both hospitals. Characteristics of patients (age, sex, primary tumor, reason for admission) and attending staff were similar between both hospitals. Mean daily equivalent doses of parenteral morphine (mg) were 44 +/- 26 and 9 +/- 10 in NA and SA, respectively (p less than 0.001). Patients in NA, received narcotics every 4 hr and on a regular basis more frequently than in SA. The types of narcotics and the use of adjuvant drugs were significantly different between NA and SA. Nonpharmacologic treatments, antiemetics, and laxatives were more frequently used in NA. These results suggest that there are significant differences in symptomatic management of advanced cancer between institutions in NA and SA.

[Eosinophilic fasciitis. Case report and review of the literature]. / Fascitis eosinofílica. Presentación de un caso y revisión de la literatura.

A case of eosinophilic fasciitis is presented. The clinical, biochemical and pathological findings were similar to those described in the literature. The history of violent exercise present in most patients was absent in our case. Immunofluorescent studies of the fascial and muscular biopsy showed deposits of C3 and fibrinogen in the vessel walls. The information of E rosettes by T lymphocytes was lowered and the intradermic reaction with PPD and PHA were negative suggesting a depletion of cell mediated immunity.

[Medical treatment of 44 patients with anal canal carcinoma. Argentinian Intergroup for the treatment of gastrointestinal tumors (IATTGI)]. / Tratamiento médico de 44 pacientes con carcinoma del conducto anal. Intergrupo Argentino para el Tratamiento de los Tumores Gastro-Intestinales (IATTGI).

In order to investigate the medical treatment of anal canal carcinoma (ACC), 27 patients (pts) were treated with cisplatin, fluorouracil and radiotherapy, in an alternating schedule. Eleven pts received mitomycin C, fluorouracil and radiotherapy, in a concurrent scheme. Finally, six pts were included in a new outpatient scheme with cisplatin, fluorouracil, leucovorin, mitomycin C and concurrent radiotherapy. Within the first schedule, 25 pts were evaluable and 18 achieved complete response. All of them are disease free until now. With the second scheme, 7/10 pts had a complete response and 5 of them are alive and disease free. All the pts included in the last schedule (6/6) achieved complete remission. There were no deaths related to toxicity. Our experience is one of the earliest in oncology using cisplatin as a first line drug, in the non-surgical treatment of ACC. We think that the use of cisplatin is feasible, its toxicity is manageable, and its effectivity is similar to other schedules, as observed in our last scheme.

Double-blind evaluation of the effects of mazindol on pain, depression, anxiety, appetite, and activity in terminal cancer patients.

In a double-blind, crossover study, mazindol (1 mg) at breakfast, lunch, and 4:00 PM was compared with a placebo to determine its efficacy for symptom control in 30 terminal cancer patients. In 26 evaluable patients, intensity of pain and analgesic consumption were significantly improved after mazindol, while anxiety, appetite, and food consumption were significantly worse. Activity and depression were not modified by mazindol. After the completion of the trial, mazindol was chosen as a more effective drug by the patients in ten cases (38%) and by the investigators in nine (35%); placebo was chosen by the patients in seven cases (27%) and by the investigators in 11 (42%). Two patients (7%) developed delirium that required discontinuation of treatment. At the present time, there are no clearcut indications for mazindol in terminal cancer patients.

Vinca alkaloid-induced cardiovascular autonomic neuropathy.

To determine the incidence of vinca alkaloid (VA)-induced cardiovascular autonomic neuropathy (CAN), neoplastic patients were studied. Thirty-three of them were receiving chemotherapy regimens including VAs, and 30 were receiving chemotherapy without VA and were considered controls. Abnormal variation in blood pressure on standing, heart rate during deep breathing, and heart rate on standing was found in 27 (82%), 16 (48%), and 16 (48%) patients receiving VA versus nine (30%; P less than 0.01), three (10%; P less than 0.05), and one (P less than 0.001) controls, respectively. Of 198 tests performed, 100 were abnormal in patients receiving VA (51%) versus 33 of 180 tests in the controls (18%; P less than 0.001). Although abnormal clinical or electrocardiographic tests for CAN appeared significantly more frequently in patients who received high doses of VA (P less than 0.01), their incidence was not significantly different in patients greater than or equal to 60 years of age, in those who received doxorubicin, or in those who showed abnormal deep tendon reflexes. The consequences of VA-induced CAN might be especially important for potentially curable cancer patients.

El tratamiento de los pacientes con carcinoma epidermoide del canal anal en los últimos 20 años en nuestro hospital / Treatment of patients with squamous cell carcinoma of the anal canal in the last 20 years in a gastroenterology hospital

Anal cancers compromise only 1.5% of all digestive tumors. At present, concurrent radiochemotherapy (RT-CT) is the treatment of choice for most of these lesions. OBJECTIVE: To collect and analyze clinical data from the medical records of all consecutive patients with squamous cell carcinoma of the anal canal (SCCAC) treated by the Oncology Section in 20 years. PATIENTS AND METHODS: The medical records of 108 patients with SCCAC were reviewed: 64% were women, mean age was 57.6 years (27-85), only 1 patient was HIV(+). RESULTS: Initial treatment: 87 patients were treated with RT-CT (81%), 5 CT only, 2 RT only, 8 local resection and 6 abdominoperineal resection (APR). 1) Patients initially treated with RT-CT: cobalt therapy was given to 76% of pts and linear accelerator was used in 24% of patients. 24% of patients received Mitomycin C based CT (modified Nigro), 66% Cisplatin based CT and 10% 5FU alone; 66% had clinical complete response (CCR) (26% of them relapsed). Median follow up was 2.16 years (1 month-15.5 years), median time to progression was 11.8 months and overall survival was 76.7% at 3 years (CI 95%: 65.2-87.7). 2) Patients initially treated with local resection: 6 patients NED and 2 relapsed (1 had CCR after RT-CT). 3) Patients initially treated with APR: 5 with curative intent (4 had local recurrence), and 1 was palliative. 4) Surgical rescue after RT-CT in 6 patients with curative intent (4 APR and 2 local resections), and in 15 patients was palliative (2 APR and other surgeries in 13). CONCLUSIONS: Our group is pioneer in the use of Cisplatin based RT-CT for the treatment of patients with SCCAC. Complete response rate and overall survival at 3 years, were similar to those reported by international data. As this is probably one of the largest series of SCCAC in Argentina, we hope that this analysis of our data would be a starting point to develop prospective clinical trials.

El carcinoma epidermoide del canal anal (CCA) constituye el 1.5% de los cánceres del sistema digestivo. Lamayoría de los pacientes puede acceder a la cura a través de radioquimioterapia (RT-QT) concurrente. Objetivos:evaluar qué ocurrió con todos los pacientes con CCA registrados por la Sección Oncología en 20 años.Pacientes y métodos: se revisaron las fichas de 108 pacientes:64% eran mujeres y la edad media fue de 57.6 años (27-83), sólo 1 paciente tenía confirmación de HIV (+). Resultados: tratamiento inicial: 87 pacientes recibieron RT-QT (81%), 5 QT sola, 2 RT sola, 8 resecciónlocal y 6 resección abdominoperineal (RAP). 1) Grupo con RT-QT de inicio: 76% realizó telecobaltoterapiay 24% acelerador lineal, 24% de los pacientes recibió un esquema con Mitomicina (Nigro modificado),66% esquemas con Cisplatino y 10% 5FU solo; respuesta clínica completa 66% (26% de ellos recidivaron).La mediana de seguimiento fue de 2.16 años (1 mes-15.5 años), la mediana de tiempo a la progresión fue de 11.8 meses y la sobrevida global fue de76.7% a los 3 años (IC 95%: 65.2-87.7). 2) Grupo con resección local de inicio: 6 pacientes sin enfermedada largo plazo y 2 recidivas (1 de ellas rescatada con RT-QT con respuesta completa). 3) RAP de inicio: 5con intención curativa (4 recidivaron localmente) y 1 paliativa. 4) Cirugía luego de RT-QT: en 6 pacientescon intención curativa (4 RAP y 2 resecciones locales), y en 15 pacientes con intención paliativa (2 RAP y 13otras cirugías). Conclusiones: nuestro grupo es pionero en el empleo de RT-QT basada en Cisplatino para eltratamiento de pacientes con CCA. Las tasas de respuesta completa y la de pacientes vivos a 3 años fueronsimilares a las reportadas en la literatura internacional. Dado que esta es probablemente la experiencia actualizada en CCA más grande de nuestro país, confiamos en que la elaboración de los datos que aquí presentamos sea el punto de partida para desarrollar ensayos clínicos prospectivos.

Prevención del cáncer colorrectal (CCR) / Prevention of colorectal cancer

Colorectal cancer (CRC) is the second leading cause of cancer death in Argentina. The cumulative lifetime risk of developing CRC for both men and women is 4-6%. Despite advances in the management of this disease, the 5-year survival rate is about 60% because only 35% of patients are diagnosed when the disease is localized. Risk factors for CRC include age, diet and life style factors, personal or family history of adenomas or CRC and personal history of inflammatory bowel disease. Scientific evidence shows that primary and secondary prevention, through screening programs, permit to reduce incidence and mortality significantly. Chemopreventive agents, including nonsteroidal antiinflammatory drugs, folate, and calcium, have been shown to have some preventive effect. Physical inactivity and excess body weight are consistent risk factors for CRC. Tobacco exposure, diet high in red meat and low in vegetables and alcohol consumption, probably in combination with a diet low in folate, appear to increase risk. The dietary fiber and risk of CRC has been studied but the results are still inconclusive. Screening for CRC is cost-effective compared with no screening, but a single optimal strategy cannot be determined from the currently available data. The advantages and disadvantages or limitations of screening modalities for CRC are analyzed. The literature and clinical practice guidelines are reviewed, with an emphasis on advances and evolving screening methods and recommendations for patients with average, moderate and high-risk CRC.

El cáncer colorrectal (CCR) ocupa el segundo lugar en mortalidad por tumores malignos en Argentina. Elriesgo de padecer un CCR a través de toda la vida es de 4-6%. A pesar de los avances en el tratamiento, la sobrevidaa 5 años del CCR se ubica en el 60% debido a que sólo el 35% de los pacientes tienen enfermedadlocalizada en el momento del diagnóstico. Los factores de riesgo incluyen la edad, dieta y estilo de vida, historia personal o familiar de adenomas o CCR y antecedentes de enfermedad inflamatoria intestinal. La evidenciacientífica permite señalar que la prevención primaria y secundaria a través de programas de pesquisapermitiría reducir la incidencia y la mortalidad significativamente. Agentes quimiopreventivos, como los antiinflamatorios no esteroideos, ácido fólico y calcio han mostrado algún efecto preventivo. El sedentarismoy el exceso de peso son convincentes factores de riesgo de CCR. El tabaco, una dieta rica en carnes rojas,pobre en vegetales y el consumo de alcohol, probablemente en combinación con una reducción de la ingestade ácido fólico, parecen incrementar el riesgo de CCR. La relación entre la ingesta de fibra y el riesgo deCCR ha sido largamente estudiada pero los resultados no son aún concluyentes. La pesquisa del CCR es costoefectivacomparada con su no realización. Se analizan las ventajas y desventajas o limitaciones de las diferentes estrategias. La literatura y las distintas normativas fueron revisadas evaluando los avances, nuevos métodosy recomendaciones para personas con riesgo promedio, moderado y alto.

Tratamiento médico de 44 pacientes con carcinoma del conducto anal. Intergrupo Argentino para el Tratamiento de los Tumores Gastro-Intestinales (IATTGI) / [Medical treatment of 44 patients with anal canal carcinoma. Argentinian Intergroup for the treatment of gastrointestinal tumors (IATTGI)]

In order to investigate the medical treatment of anal canal carcinoma (ACC), 27 patients (pts) were treated with cisplatin, fluorouracil and radiotherapy, in an alternating schedule. Eleven pts received mitomycin C, fluorouracil and radiotherapy, in a concurrent scheme. Finally, six pts were included in a new outpatient scheme with cisplatin, fluorouracil, leucovorin, mitomycin C and concurrent radiotherapy. Within the first schedule, 25 pts were evaluable and 18 achieved complete response. All of them are disease free until now. With the second scheme, 7/10 pts had a complete response and 5 of them are alive and disease free. All the pts included in the last schedule (6/6) achieved complete remission. There were no deaths related to toxicity. Our experience is one of the earliest in oncology using cisplatin as a first line drug, in the non-surgical treatment of ACC. We think that the use of cisplatin is feasible, its toxicity is manageable, and its effectivity is similar to other schedules, as observed in our last scheme.