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Cervical cancer is the seventh most frequent cancer worldwide but more than 80% of cases occur in developing countries. Till date, radiation therapy with external beam and brachytherapy remains as the core treatment for most stages of cervical cancer. However, radiation treatment protocols and equipment modelled on the best developed countries can be seldom applied directly to developing countries owing to financial constraints and lack of qualified personnel, thus, a substantial proportion of patients do not have access to even palliative radiation therapy. Treatment options when the standard therapy is either not available or difficult to reproduce in particular settings is highly desirable with the potential to save lives that otherwise could be lost by the lack of adequate treatment. These options of treatment ideally had to have show, 1) that these are not inferior to the "standard" in terms of either survival or quality of life; 2) that these can be delivered in settings were the "standard" is not available or if available its quality is poor; and 3) that the treatment option be accepted by the population to be treated. Based on these considerations, it is obvious that cervical cancer patients, particularly those who live in countries with limited resources and therefore may not have sufficient radiation therapy resources are in need of newer therapeutical options. There is now a considerable amount of information emanating from clinical studies where surgery has a major role in treating this disease. These forms of "radiation-sparing" treatments include total mesometrial resection that could make unnecessary the use of adjuvant radiation; neoadjuvant chemotherapy that could avoid the use of adjuvant radiation in around 85% of patients and preoperative chemoradiation that could make brachytherapy dispensable. The feasibility and therapeutical value of these potential forms of management need to be prospectively evaluated.
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BACKGROUND: Globally, cervical cancer primarily affects socially disadvantaged women. Five randomized trials were the foundation for adopting cisplatin-based chemotherapy during radiation as the standard of care for high-risk patients after primary radical hysterectomy who require adjuvant radiation and for locally advanced patients treated with definitive radiation. These results were obtained in clinical trials performed in carefully prepared academic centers; hence, we sought to determine whether these results could be reproduced when patients were treated on an out-of-protocol basis. METHODS: We reviewed the files of 294 patients with locally advanced cervical cancer who received radiation plus weekly cisplatin as routine management between 1999 to 2003, and analyzed treatment compliance, response rate, toxicity, and survival. RESULTS: A total of 294 patients who received radiation and cisplatin were analyzed. Mean age was 43.8 years (range, 26-68 years). The majority of cases were squamous cell carcinoma (87.8%), and distribution according to International Federation of Gynecology and Obstetrics (FIGO) stage was as follows: IB2-IIA, 23%; IIB, 53.3%, and IIIB, 23%; there were only two IVA cases. Overall, 96% of patients completed external beam, and intracavitary therapy. The majority of patients (67%) received the planned six courses of weekly cisplatin. Complete responses were achieved in 243 (83%) patients, whereas 51 (17%) had either persistent (32 patients, 10.8%) or progressive (19 patients, 6.4%) disease. At median follow-up (28 months; range, 2-68 months), 36 patients (12.2%) have relapsed (locally 30.5, and systemically, 69.5%). The most common toxicities were hematologic and gastrointestinal, in the majority of cases considered mild-moderate. At median follow-up (28 months; range, 2-68 months), overall and progression-free survival are 76.5 and 67%, respectively. CONCLUSION: Our results support use of chemoradiation with six weekly applications of cisplatin at 40 mg/m2 during external radiation for routine management of locally advanced cervical cancer.
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BACKGROUND: Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection. METHODS: Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method. RESULTS: Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration. CONCLUSION: Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Adulto , Antimetabólitos Antineoplásicos/farmacologia , Antineoplásicos/farmacologia , Área Sob a Curva , Carboplatina/farmacologia , Cisplatino/farmacologia , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Intervalo Livre de Doença , Feminino , Fluoruracila/farmacologia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Exenteração Pélvica , Projetos Piloto , Recidiva , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , GencitabinaRESUMO
PURPOSE: To compare gemcitabine and cisplatin (GC) with cisplatin (C) concurrent with radiotherapy in International Federation of Gynecology and Obstetrics Stage IB2, IIA, and IIB cervical carcinoma in a preoperative setting. The main endpoints were the pathologic response rate and toxicity. METHODS AND MATERIALS: A total of 83 patients were randomized to either C or GC. Treatment consisted of six doses of cisplatin at 40 mg/m(2) every week for Arm 1 (C) and six doses of gemcitabine at 125 mg/m(2) plus cisplatin at 40 mg/m(2) every week for or Arm 2 (GC) Both regimens were administered concurrent with 50 Gy of external beam radiotherapy in 2-Gy fractions for 5 weeks. After chemoradiotherapy, patients underwent radical hysterectomy. RESULTS: All 83 patients were studied for toxicity and 80 for response. The complete pathologic response rate in the C arm and GC arm was 55% (95% confidence interval, 35.5-73%) and 77.5% (95% confidence interval, 57-90%; p = 0.0201). Among those with a partial response, 7 patients each had high and intermediate-high risk factors for recurrence in their surgical specimens in the C arm vs. 2 and 3 patients, respectively, with these characteristics in the CG arm. The number of weekly doses and the dose intensity of GC were lower than for C. The time to complete external beam radiotherapy also favored the C arm. The CG combination produced greater GI and hematologic toxicity. CONCLUSION: The radiosensitizing combination of GC achieved a greater pathologic response rate than C in the treatment of cervical cancer.
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Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Radiossensibilizantes/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Intervalos de Confiança , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Radiossensibilizantes/efeitos adversos , Dosagem Radioterapêutica , Neoplasias do Colo do Útero/patologia , GencitabinaRESUMO
PURPOSE: Chemoradiation based on cisplatin, most commonly weekly, is the standard treatment of locally advanced cervical cancer; however, the nephrotoxic potential and the requirement for hydration of cisplatin somewhat restrains its use. The objective of this study was to determine the recommended dose of carboplatin when administered weekly during pelvic radiation (RT). METHODS AND MATERIALS: Twenty-four histologically proven, International Federation of Gynecology and Obstetrics Stage IIIB patients were treated with standard pelvic RT concurrently with six weekly applications of carboplatin at the following dose levels: 100 mg/m(2), 116 mg/m(2), 133 mg/m(2), and 150 mg/m(2). Six patients per level were treated. Acute toxicity was assessed according to the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring Criteria. The recommended dose was defined as the one that was one level below the level at which dose-limiting toxicity was present in more than one-third of patients. RESULTS: Between September 2001 and July 2002, 24 patients were accrued. All but two completed external beam radiotherapy and intracavitary treatment. The treatment was well tolerated. The median number of weekly applications of carboplatin was six, and the mean dose to points A and B was 85.6 Gy (range 75.2-91.6) and 62.9 Gy (range 58.2-74.6), respectively. RT was delivered within 41.7 days (range 33-70). Dose-limiting toxicity (leukopenia and/or neutropenia) was present in 50% of patients treated at the higher dose level (150 mg/m(2)). At the recommended dose of 133 mg/m(2), 33% of patients presented with Grade 3 leukopenia. At treatment completion, 75% of patients had a complete clinical response. CONCLUSION: Carboplatin at 133 mg/m(2), weekly for 6 weeks, is a well tolerated and effective radiosensitizer in cervical cancer patients.
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Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Carboplatina/efeitos adversos , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias do Colo do Útero/patologiaRESUMO
Induction chemotherapy followed by surgery, particularly with newer agents or combinations, remains to be explored in locally advanced cervical cancer. Gemcitabine cisplatin is a very active combination for this tumor, therefore we explored the activity of gemcitabine in combination with oxaliplatin. Ten untreated patients with histologic diagnosis of cervical carcinoma and staged as IB2 to IIIB were treated with 3 21-day courses of oxaliplatin 130 mg/m day 1 and gemcitabine 1,250 mg/m days 1 and 8 followed by locoregional treatment with either surgery or concomitant chemoradiation. Response and toxicity were evaluated at the end of chemotherapy. All patients were evaluable. The overall clinical response rate was 80%, being complete in 3 patients (30%) and partial in 5 (50%). Seven (70%) patients underwent surgery, and three (30%) had chemoradiation as definitive treatment. Hematologic toxicity was moderate, with leukopenia grades III-IV in 17 and 0%; granulocytopenia grades III-IV in 23 and 3%, respectively. Eight patients had grade I oropharyngeal toxicity. At a median follow-up of 11 months (range: 10-12), all patients are disease free. Gemcitabine oxaliplatin is a very active and well-tolerated combination for locally advanced cervical cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias do Colo do Útero/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adulto , Carcinoma Adenoescamoso/tratamento farmacológico , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/radioterapia , Carcinoma Adenoescamoso/cirurgia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Desoxicitidina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , GencitabinaRESUMO
El vómito y la náusea inducida por agentes citotóxicos frecuentemente limita la utilización de agentes efectivos pero emetizantes como el cisplatino. Este fue un estudio comparativo de Granisetron versus metoclopramida más dexametasona que evaluó la eficacia y efectos colaterales en las primeras 24 horas en ambos grupos. Se incluyeron 40 pacientes con diagnóstico de cáncer candidatos a recibir cisplatino a una dosis mayor de 49 mg/m2 con hoja de consentimiento informado. Se excluyeron pacientes que hubieran tenido náusea o vómito previo al tratamiento. Se administró Granisetron 40 m g/kg diluido en 20 mL de la solución salina para infusión intravenosa de cinco minutos previo a cisplatino en un grupo y en el otro se administró dexametasona 12 mg diluidos en 50 mL de solución salina para infusión de 30 minutos y metoclopramida 3 mg/kg I.V. en 30 minutos seguido de 4 mg/kg en infusión intravenosa para 8 hrs. Se consideró respuesta completa cuando los pacientes no tuvieron vómito ni náusea o sólo náusea leve. Hubo veintiún pacientes en el grupo de Granisetron y 19 en el grupo de tratamiento estándar. Obtuvimos respuesta completa (RC) del 66.6 por ciento en el grupo de Granisetron vs 73.68 por ciento en el grupo control, se presentó 20 por ciento de extrapiramidalismo de intensidad moderada en el grupo control (p=0.89), mientras que sólo el 9.5 por ciento del grupo de Granisetron presentó cefalea. Granisetron fue tan eficaz como la combinación con metoclopramida con la ventaja de tener muy pocos efectos adversos.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Cisplatino , Dexametasona , Granisetron , Metoclopramida , Antieméticos/farmacologiaRESUMO
Gemcitabina es un agente activo en el tratamiento del cáncer de pulmón (CPCNP). El tratamiento semanal con gemcitabina, como agente único, ha mostrado respuestas del 20 al 26 por ciento. Este estudio fase 2 fue realizado para determinar la eficacia y seguridad de gemcitabina 1000 mg/m2, administrado semanalmente. Por tres semanas, seguido de una de descanso (ciclos de 28 días): los pacientes requirieron tener evidencia histológica de CPCNP y enfermedad avanzada; estado de desempeño de Zubrod de 0 a 2 y enfermedad medible. No se permitió que hubieran recibido tratamiento previo. Veinte pacientes, diez hombres y diez mujeres con una edad promedio de 60 años fueron incluidos en el estudio. La mayor parte de los pacientes (doce pacientes, 60 por ciento) tuvieron EC IIIb y, diagnóstico de adenocarcinoma (trece pacientes, 65 por ciento). Cuatro pacientes (20 por ciento) tuvieron EC IIIa y otros cuatro (20 por ciento) tuvieron EC IV, siete pacientes (35 por ciento) tuvieron variedad histológica epidermoide. Los pacientes recibieron un total de 62 ciclos y un promedio de 3.1 ciclos de terapia con gemcitabina. De los dieciocho pacientes que se incluyeron para evaluar eficacia, en seis se obtuvo respuesta parcial con un porcentaje de respuesta del 33.3 por ciento. La supervivencia media fue de siete meses (dos a 15 meses) con un tiempo medio libre de enfermedad de 3.5 m (1-15 meses) y un año de supervivencia del 22.2 por ciento. Toxicidad hematológica grado 3 y 4 de la Organización Mundial de la Salud (OMS) fue observada en menos del 2 por ciento de todos los ciclos. La toxicidad más común grado 3 y 4 no hematológica fue náusea y vómito observada en menos del 5 por ciento de los ciclos. Elevación transitoria de transaminasas se observó en menos del 4 por ciento de los ciclos. Un paciente presentó hepatitis fulminante y rash generalizado que, a consideración de los investigadores, se debió a una reacción de hipersensibilidad por toxicidad de la gemcitabina. En conclusión, gemcitabina como agente único en administración semanal de 1000 mg/m2 es segura y efectiva en el tratamiento del CPCNP avanzado.