Raquel Gerson

Chemotherapy with gemcitabine in advanced biliary tract carcinoma.

BACKGROUND Biliary tract carcinoma is infrequent; usually majority of cases are detected in an advanced phase of the disease, thus surgical resection is not feasible and prognosis is poor, mean survival is 6 months and, chemotherapy is the main therapeutic option. OBJECTIVE An overall review of all clinical trials published regarding gemcitabine, alone or in combination, as a treatment in advanced biliary tract carcinoma. RESULTS Gemcitabine has been reported as a single drug, in 12 trials and as a combination in 21 studies. As a single agent it has been evaluated in a 30 minute infusion, biweekly administration, fixed infusion [10 mg/m2/min] or as a prolonged infusion [24 hours]. Objective response has been reported between 0 and 36%, stable disease 13 to 15%, time to progression 2 - 10.7 months, overall survival 4 to 14 months. Chemotherapy combinations based on gemcitabine have been evaluated with several agents, among them were 5-FU, mitomycin oxaliplatin, capecitabine, cisplatin, docetaxel and irinotecan; the objective response seen: 9.3% to 64%, stable disease 9.3% to 53%, time to progression 3 - 10 months and overall survival 4.7 to 18 months. CONCLUSION Gemcitabine is an effective drug in advanced biliary tract carcinoma with a low toxicity profile. It should be considered as the standard treatment for unresectable or metastatic disease while awaiting phase III results.

ACUTE PANCREATITIS SECONDARY TO IFOSFAMIDE

Acute pancreatitis in cancer patients can be secondary to the malignant process itself. It is also a rare complication of antineoplastic agent administration. Ifosfamide is an effective drug in the treatment of several tumors and has known neurologic, renal, and hematologic toxicities. There is only one recent report in the literature of pancreatitis associated with ifosfamide. We report a case of a 65-year-old woman with small cell bronchogenic carcinoma without pancreatic metastases who developed acute pancreatitis after ifosfamide administration.

Respuesta terapéutica a gemcitabina en cáncer de mama avanzado en relación con factores immunohistoquímicos

ResumenEl cáncer de mama avanzado tiene un pronóstico pobre. La gemcitabina, análogo de la desoxycitidina, muestra índices de resquesta entre el 25% y 37% en casos avanzados. Hemos evaluado la toxicidad y la eficacia de la gemcitabina en pacientes con cáncer de mama avanzado, previamente tratados y correlacionado las respuestas con los factores inmunohistoquímicos. Los pacientes fueron tratados con gemcitabina a dosis de 1.250 mg/m2 durante tres semanas cada mes por al menos dos ciclos. Se evaluó edad, HER2/neu,p53, receptores hormonales, angiogénesis, sitios y número de metástasis, número de ciclos recibidos, escala de Karnofsky, tiempo libre de progresión, sobrevida global y efectos adversos. De enero de 1996 a noviembre de 1999 se incluyeron 19 mujeres con edad promedio 52,3±12,7; rango: 31 a 84 años. Los factores immunohistoquímicos fueron determinados en 10 pacientes; el 56,2% resultaron positivos. La sobreexpresión del HER2/neu se encontró en 5 pacientes,p53 en 5, receptores de estrógenos en 4 y progesterona en tres. La gemcitabina fue administrada como segunda línea terapéutica en 6 pacientes, tercera en 6, cuarta en 3, quinta en uno y sexta en uno. La escala de Karnosfky promedio al inicio del tratamiento fue de 81,05±11; rango; 70 a 100; después del segundo o tercer ciclo fue de 82,1±11,3 (60 a 100) y al final 78,9±11,5 (60 a 100), p=0,666. Los pacientes recibieron de 2 a 10 ciclos de tratamiento. El número de sitios con metástasis fue 2,7±1,2; rango: 1 a 5. Se observaron dos respuestas completas (10,5%), parciales 6 (31,5%), índice de respuesta 42% y estatismo 7 y progresión en 4. El tiempo libre de progresión promedio fue de 8,5±4,8 meses (2 a 19). La sobrevida global fue de 10,4±6,8 meses (2 a 23). Catorce pacientes murieron con actividad tumoral (73,6%); 4 se encuentran vivos con actividad (21%) y uno sin actividad. No identificanos relación entre la respuesta tumoral y los factores inmunohistoquímicos HER2/neu, p=0,519;p53, p=0,519; receptores estrogénicos, 0,236, y de progesterona, 0,673. Se observaron efectos adversos en 9 pacientes, trombocitopenia grado I-II en 7, anemia grados II-III en 5 y neutropenia grados II-III en tres. Náusea y vómito, disuria y alopecia en dos pacientes. La gemcitabina muestra ser activa en pacientes con cáncer de mama avanzado previamente tratados, con bajo grado de efectos adversos. No se mostró relación entre las respuestas tumorales y los factores immunohistoquímicos.AbstractAdvanced breast cancer has a poor prognosis. Gemcitabine, a desoxycitidine analogue, has shown 25% to 37% overall response in advanced cases. We have evaluated the efficacy and safety of gemcitabine in patients with advanced breast cancer heavily pretreated and to correlated responses with immunohistochemical factors. Patients were treated at doses of 1,250 mg/m2/week/q/month, for at least two cycles. Age, HER2/neu,p53, hormonal receptors, angiogenesis, site and number of metastases, number of cycles received, Karnofskys score, progression free survival, overall survival and side effects were evaluated.From January 1996 to November 1999, 19 women were included, mean age 52.3±12.7; range: 31 to 84 years. Immunohistochemical factors were determined in 10 patients and resulted positive 52.6%; overexpression of c-erbB-2 in 5 patients,p53 in 5, estrogen receptor in 4, progesterone receptor in 3. Gemcitabine was applied as second line in 6 patients, third in 6, fourth in 3, fifth in one and sixth in one too. Mean Karnofsky score at the start of treatment 81.05±11; range: 70 to 100: after second and third cycles 82.1±11.3 (60–100) and at the end 78.9±11.5 (60–100); p=0.666. Patients received 2–10 cycles of treatment. Mean metastasic sites 2.7±1.2; range: 1 to 5; two complete responses, 10.5%; partial 6 (31.5%), response rate 42%, stable 7 and progression 4. Progression free survival 8.5±4.8 months, range 2 to 19. Overall survival 10.4±6.8 mos, two to 23. Forteen patients have died with tumor (73.6%), 4 are alive with tumor (21%); and only one is alive without tumor. We did not identify relationship between tumor response and immunohistochemical factors, c-erbB-2, p=0.519;p53, p=0.519; estrogen receptor, p=0.236 and progesterone receptor; p=0.673. Side effects were observed in 9, thrombocytopenia grade I-II in 5 patients, neutropenia grade I-II in 7 and anemia grade II-III in 3. Nausea, vomiting, dysuria and alopecia in two patients.Gemcitabine is active in heavily pretreated advanced breast cancer patients showing low grade side effects. Apparently, there is not relationship between tumor response and immunohistochemical factors.