RESUMEN
BACKGROUND: Colorectal cancer is common worldwide and chemoprevention has the potential of reducing the number of individuals who may suffer and perish from this disease. METHODS: A randomized placebo controlled pilot study in colorectal cancer patients was performed using calcium carbonate as the test agent in a multi-institutional oncology study group. RESULTS: Two hundred twenty volunteers were randomized in the study. The primary goals of compliance, accrual, and toxicity monitoring are presented. Presence of multiple adenomas at study entry and subsequent development of metachronous adenomas were recorded and found to be associated with synchronous adenomas. The secondary endpoint of recurrent adenomas indicated lower rates of new adenoma in the volunteers randomized to the calcium group. CONCLUSION: This pilot study indicates the feasibility of enrolling survivors of colorectal cancer as study volunteers in a colorectal neoplasm chemoprevention clinical trial and oral calcium continues to be a potentially effective drug in reducing colorectal adenomas.
Asunto(s)
Adenoma/prevención & control , Antiácidos/uso terapéutico , Carbonato de Calcio/uso terapéutico , Neoplasias Colorrectales/prevención & control , Recurrencia Local de Neoplasia/prevención & control , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies. Preclinical and early clinical evidence has supported targeting the epidermal growth factor receptor (EGFR) signaling pathway in patients with pancreas cancer. This trial was conducted to evaluate the contribution of an EGFR-targeted agent to standard gemcitabine therapy. Cetuximab is a monoclonal antibody against the ligand-binding domain of the receptor. PATIENTS AND METHODS: Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine alone or gemcitabine plus cetuximab. The primary end point was overall survival. Secondary end points included progression-free survival, time to treatment failure, objective response, and toxicity. RESULTS: A total of 745 eligible patients were accrued. No significant difference was seen between the two arms of the study with respect to the median survival time (6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm; hazard ratio = 1.06; 95% CI, 0.91 to 1.23; P = .23, one-sided). Objective responses and progression-free survival were similar in both arms of the study. Although time to treatment failure was longer in patients on gemcitabine plus cetuximab (P = .006), the difference in length of treatment was only 2 weeks longer in the combination arm. Among patients who were studied for tumoral EGFR expression, 90% were positive, with no treatment benefit detected in this patient subset. CONCLUSION: In patients with advanced pancreas cancer, the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone. Alternate targets other than EGFR should be evaluated for new drug development.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cetuximab , Desoxicitidina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , GemcitabinaRESUMEN
OBJECTIVE: While primary cisplatin-based intraperitoneal chemotherapy has been shown to favorably impact survival in small-volume residual advanced ovarian cancer, there is a need to develop strategies that improve the effectiveness of this approach. METHODS: A multi-center phase 2 trial was conducted that added intravenous pegylated liposomal doxorubicin (day 8; 30-40 mg/m(2)) to a regimen of intraperitoneal cisplatin (day 2; 75 mg/m(2)) and intravenous (day 1; 135 mg/m(2)) plus intraperitoneal (day 8; 60 mg/m(2)) paclitaxel. Treatment was initially delivered on an every 3-week schedule, but was modified to an every 4-week program due to excessive toxicity. Patients were to receive 6 cycles of this regimen. RESULTS: Of 68 patients entering this trial, 63 patients were eligible and evaluable, of whom 39 (62%) completed 6 cycles. Overall, 32 (51%) experienced at least 1 grade 4 or worse toxicity (most commonly hematologic) including 5 treatment-related deaths. Median progression-free survival (PFS) was 25 months (2-year PFS: 52%) and median overall survival 51 months, an outcome similar to previous reports of cisplatin-based intraperitoneal chemotherapy in comparable patient populations. Seventeen patients (27% of all eligible patients) were without evidence of disease recurrence >4 years following entry into the trial. CONCLUSION: Both the overall trial outcome, and specifically the excessively severe systemic toxicity of this regimen would prevent its future development in this exact form. The provocative PFS in a subset of individuals should encourage the development of alternative strategies designed to optimize the delivery of regional therapy in ovarian cancer management.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Femenino , Humanos , Infusiones Intravenosas , Infusiones Parenterales , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Polietilenglicoles/administración & dosificaciónRESUMEN
BACKGROUND: The poor prognosis reported for patients with high-grade glial neoplasms indicates a need for the development of multimodality therapeutic approaches. The addition of chemotherapy has contributed variably to increased survival. The objective of the current study (Southwest Oncology Group [SWOG] 9016) was to determine whether concurrent radiotherapy and chemotherapy with the combination of carmustine and cisplatin could be given safely in a cooperative group setting. Additional objectives included the estimation of response rate, the rate of disease stabilization, and the probability of 1-year survival. METHODS: SWOG 9016 study included 59 eligible patients with grade III or IV astrocytoma who received radiotherapy concurrently with carmustine/cisplatin chemotherapy. Patients were required to have either measurable or evaluable disease. The therapeutic endpoints were comprised of complete response (CR), partial response (PR), or progressive disease (PD). RESULTS: Six patients achieved a CR (CR rate of 10%; 95% confidence interval [95% CI], 4-21%), 4 achieved a PR (PR rate of 7%; 95% CI, 2-16%), and 2 patients (3%) experienced an unconfirmed response. Twenty-four patients (41%; 95% CI, 28-54%) had stable disease and 10 patients (17%) demonstrated PD. The overall disease stabilization rate (CR + PR + stable disease, excluding unconfirmed response) was 58% (95% CI, 44-70%). CONCLUSIONS: Despite the presence of a cohort of long-term survivors, the results of the current study do not appear to support the additional study or routine use of concurrent cisplatin and carmustine.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Carmustina/administración & dosificación , Cisplatino/administración & dosificación , Glioma/tratamiento farmacológico , Glioma/radioterapia , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Carmustina/efectos adversos , Cisplatino/efectos adversos , Terapia Combinada , Femenino , Glioma/mortalidad , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Radioterapia Conformacional/métodos , Sudoeste de Estados Unidos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Many patients with invasive urothelial cell cancer are poor candidates for cisplatin-based chemotherapy, and many are high risk for cystectomy. Southwest Oncology Group Trial 8733 was designed to address treatment for such patients. METHODS: Eligible patients had primary or recurrent muscle-invasive disease with transitional cell or squamous cell histology, a performance status from 0 to 2, no extrapelvic disease, a life expectancy >3 months, and adequate hematologic function. The treating clinician assigned patients to operable or inoperable groups. All patients received 2 cycles of 5-fluorouracil (5-FU) at a dose of 1000 mg/m(2) per day x 4 starting concurrently with radiation at a dose of 200 centigrays per day x 10 each cycle. After 2 cycles, operable patients with positive biopsies underwent cystectomy, and patients with negative biopsies received a third cycle of chemoradiotherapy. Patients in the inoperable group received 3 cycles without interim biopsy. RESULTS: Eighteen of 24 eligible patients in the operable group were evaluable for response. Five patients had a complete response (CR), 9 patients had stable disease, 1 patient had progressive disease, and 3 patients were not assessable. The median progression-free survival was 10 months (95% confidence interval [95% CI], 4-14 months), and the median overall survival was 18 months (95% CI, 7-28 months). In the inoperable group, 35 of 37 eligible patients were evaluable for response with 17 CRs (49%; 95% CI, 31%-66%). The median progression-free survival was 13 months (95% CI, 10-17 months), and the median overall survival was 20 months (95% CI, 11-53 months). There were no episodes of grade 4 toxicity. CONCLUSIONS: In the current study, the combination of 5-FU and radiation was found to be tolerated well by patients with numerous comorbidities who could not tolerate cisplatin-based therapy or cystectomy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cistectomía , Neoplasias de los Músculos/terapia , Terapia Neoadyuvante , Neoplasias de la Vejiga Urinaria/terapia , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/radioterapia , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/terapia , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Terapia Combinada , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Neoplasias de los Músculos/tratamiento farmacológico , Neoplasias de los Músculos/radioterapia , Neoplasias de los Músculos/cirugía , Pronóstico , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/cirugía , Vinblastina/administración & dosificaciónRESUMEN
Inhibition of DNA excision repair can modulate resistance to cisplatin. Cytosine arabinoside (Ara-C) and hydroxyurea (HU), in combination, inhibit the excision-repair system and removal of platinum-DNA adducts. Marked cytotoxic synergy had been demonstrated in vitro at clinically achievable levels. The three-drug regimen was found to be feasible in clinical pilot studies. A Phase II study in patients with relapsed or progressive anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) was performed in the Southwest Oncology Group. The primary end point was 6 month survival, historically about 42%. A loading dose of HU 1,260 mg/m2 IV over 1 h was followed by Ara-C 1,200 mg/m2 plus HU 5,040 mg/m2 IV over 12 h, followed by cisplatin 100 mg/m2 IV over 1 h. A total of 76 patients were registered. The GBM stratum registered 56 patients in a two-stage accrual. Among 51 eligible GBM patients, the 6-month survival probability was 41% (95% CI 28-55%), and median overall survival was 5 months (95% CI 4-6 months). The 6-month progression-free survival probability was 25% (95% CI 14-37%), and median progression-free survival was 2 months (95% CI 2-4 months). One patient achieved a partial response (2%, 95% CI 0-10%), 13 patients had stable disease (25%, 95% CI 14-39%). Twenty-two patients progressed, and 14 were not assessable for response. The AA stratum was closed early after 20 patients due to slow accrual. Among 19 eligible patients, the 6-month survival probability was 58% (95% CI 36-80%), and median overall survival was 7 months (95% CI 7-14 months). The 6-month progression-free survival probability was 26% (95% CI 6-46%), and median progression-free survival was 3 months (95% CI 2-5 months). No responses were seen. Six patients (32%) had stable disease (95% CI 13-57%), 11 progressed, and 2 were not assessable for response. Of the 70 patients evaluable for toxicity, two died of infection. Twenty-three patients (33%) experienced Grade 4 toxicities, primarily hematological. Cisplatin combined with HU and Ara-C did not improve the 6 month survival rate in patients with relapsed or progressive AA or GBM. Significantly more hematological toxicity was seen than expected from cisplatin alone. Although benefit might be possible in a more platinum-sensitive tumor type, further clinical trials with this regimen for patients with glioblastoma multiforme or anaplastic astrocytoma are not justified.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Cisplatino/uso terapéutico , Citarabina/uso terapéutico , Glioma/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Supervivencia sin Enfermedad , Glioma/mortalidad , Humanos , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
PURPOSE: Malignant pleural mesothelioma (MPM) expresses high levels of epidermal growth factor receptor (EGFR), and preclinical studies have identified antitumor activity of EGFR tyrosine kinase inhibitors (TKIs) in MPM. We conducted a phase II trial of the EGFR TKI erlotinib in previously untreated patients with MPM. PATIENTS AND METHODS: Patients with measurable and nonmeasurable disease were treated with erlotinib 150 mg/d on days 1 through 28 of each 28-day dosing cycle. Archived patient tumors were analyzed for immunohistochemical expression of EGFR, phospho-EGFR, human epidermal growth factor receptor 2 (HER2), phospho-extracellular signal-regulated kinase (ERK), and phosphatase and tensin homolog (PTEN) and phosphorylation of members of the phosphatidylinositol 3-kinase/Akt signaling pathway. RESULTS: Sixty-three patients were treated on the study. EGFR was highly expressed in 75% of patient tumors, as was phospho-ERK (82%), phospho-Akt (84%), phospho-mammalian target of rapamycin (74%), and phospho-forkhead (74%). HER2 was rarely expressed, and loss of PTEN was rare. For 33 patients with measurable disease, there were no objective responses; 14 patients (42%) had stable disease, 15 patients (45%) had disease progression, and four patients had inadequate assessments to determine response. Toxicities were mainly constitutional (51%), dermatologic (82%), and GI (52%); there was one death on trial, which was related to dyspnea. Median overall survival time was 10 months; 1-year survival rate was 43%; and median progression-free survival time was 2 months. CONCLUSION: Single-agent erlotinib was not effective in MPM, despite high expression of EGFR. Activation of the ERK and phosphatidylinositol 3-kinase/Akt downstream pathways are possible resistance mechanisms to EGFR TKI. The activated phosphatidylinositol 3-kinase/Akt pathway is a potential therapeutic target for MPM.
Asunto(s)
Antineoplásicos/uso terapéutico , Mesotelioma/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológico , Quinazolinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Receptores ErbB/metabolismo , Clorhidrato de Erlotinib , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Mesotelioma/metabolismo , Mesotelioma/mortalidad , Persona de Mediana Edad , Neoplasias Pleurales/metabolismo , Neoplasias Pleurales/mortalidad , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Resultado del TratamientoRESUMEN
PURPOSE: The purpose of this Phase II multi-institutional trial was to determine the efficacy and toxicity of R115777 in previously untreated patients with metastatic colorectal carcinoma. PATIENTS AND METHODS: Patients were required to have histologically confirmed colorectal cancer with distant metastatic disease that was not surgically curable. They could not have received prior chemotherapy for metastatic disease. R115777 was given at a dose of 300 mg p.o. twice a day for 21 days every 28 days until tumor progression or toxicity or other reason for discontinuation occurred. The primary endpoint was to determine the confirmed response probability with this treatment. RESULTS: There were 55 eligible patients accrued to the study. There were no complete responses, but one confirmed partial response for a confirmed response probability of 2% (95%CI 0-10%). Three additional patients had an unconfirmed partial response for an overall response probability of 7%. The time to treatment failure was 1.7 months and the estimated median survival was 8.1 months. One patient died of treatment related infection and there were 7 other patients with grade 4 toxicities consisting of neutropenia, leukopenia, febrile neutropenia and thrombocytopenia, depression, increased bilirubin, anemia, and pneumonitis/infiltrates. CONCLUSION: R115777 given as a single agent by this dose and schedule is ineffective in patients with metastatic colorectal cancer.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Quinolonas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Quinolonas/efectos adversos , Sudoeste de Estados Unidos , Análisis de SupervivenciaRESUMEN
PURPOSE: The purpose of this Phase II multi-institutional study was to define the efficacy and toxicity of ixabepilone in patients with advance pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients were required to have pancreatic adenocarcinoma and metastatic or recurrent disease that was not amenable to curative resection. Performance status was 0-1, and patients could not have had prior chemotherapy, or chemoradiation therapy for their advanced disease although prior local palliative radiation was allowed. Ixabepilone was administered iv as a 3 hour infusion every 21 days. Initially, the dose was 50 mg/m(2) but this was lowered to 40 mg/m(2) shortly after the trial opened because of concerns about neurotoxicity. RESULTS: Sixty-two patients were registered however 2 were ineligible because they did not have recurrent or metastatic disease. For the 60 eligible patients, 22 had performance status of 0 and 38 performance status of 1. The estimated 6-month survival was 60% (95% CI 48%-72%) with a median survival of 7.2 months and an estimated time to treatment failure of 2.3 months. Out of 56 patients with measurable disease there were 5 confirmed partial responses for a confirmed response probability of 9% (95% CI 3%-20%) and 7 unconfirmed partial responses for an overall response probability of 21% (95% CI 12%-34%). Common toxicities were neutropenia/granulocytopenia, nausea and vomiting and neuropathy. There was one death, cause not determined but judged "possibly" related to treatment. CONCLUSION: Ixabepilone shows encouraging activity in patients with advanced pancreatic cancer and should be investigated further in this disease.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Epotilonas/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Moduladores de Tubulina/uso terapéutico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Epotilonas/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Análisis de Supervivencia , Resultado del Tratamiento , Moduladores de Tubulina/efectos adversosRESUMEN
PURPOSE: We evaluated the efficacy of cyclophosphamide, methotrexate, and fluorouracil (CMF) versus cyclophosphamide, doxorubicin, and fluorouracil (CAF) in node-negative breast cancer patients with and without tamoxifen (TAM), overall and by hormone receptor (HR) status. PATIENTS AND METHODS: Node-negative patients identified by tumor size (> 2 cm), negative HR, or high S-phase fraction (n = 2,690) were randomly assigned to CMF, CAF, CMF + TAM (CMFT), or CAF + TAM (CAFT). Cox regression evaluated overall survival (OS) and disease-free survival (DFS) for CAF versus CMF and TAM versus no TAM separately. Two-sided CIs and one-sided P values for planned comparisons were calculated. RESULTS: Ten-year estimates indicated that CAF was not significantly better than CMF (P = .13) for the primary outcome of DFS (77% v 75%; HR = 1.09; 95% CI, 0.94 to 1.27). CAF had slightly better OS than CMF (85% v 82%, HR = 1.19 for CMF v CAF; 95% CI, 0.99 to 1.43); values were statistically significant in the planned one-sided test (P = .03). Toxicity was greater with CAF and did not increase with TAM. Overall, TAM had no benefit (DFS, P = .16; OS, P = .37), but the TAM effect differed by HR groups. For HR-positive patients, TAM was beneficial (DFS, HR = 1.32 for no TAM v TAM; 95% CI, 1.09 to 1.61; P = .003; OS, HR = 1.26; 95% CI, 0.99 to 1.61; P = .03), but not for HR-negative patients (DFS, HR = 0.81 for no TAM v TAM; 95% CI, 0.64 to 1.03; OS, HR = 0.79; 95% CI, 0.60 to 1.05). CONCLUSION: CAF did not improve DFS compared with CMF; there was a slight effect on OS. Given greater toxicity, we cannot conclude CAF to be superior to CMF. TAM is effective in HR-positive disease, but not in HR-negative disease.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Metotrexato/administración & dosificación , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Análisis de Supervivencia , Tamoxifeno/administración & dosificaciónRESUMEN
PURPOSE: Modest toxicity and possibly enhanced activity makes continuous-infusion fluorouracil (FU) an attractive alternative to FU plus leucovorin (FU/LV) for the adjuvant treatment of colorectal cancer. Intergroup trial 0153 (Southwest Oncology Group trial 9415) was developed to compare the efficacy of continuous-infusion FU (CIFU) plus levamisole to FU/LV plus levamisole in the adjuvant treatment of high-risk Dukes' B2 and C1 or C2 colon cancer. PATIENTS AND METHODS: After surgery, patients were randomly assigned to CIFU 250 mg/m(2)/d for 56 days every 9 weeks for three cycles or FU 425 mg/m(2) and LV 20 mg/m(2) daily for 5 days every 28 to 35 days for six cycles. All patients received levamisole 50 mg tid for 3 days every other week. The primary end point was overall survival (OS). RESULTS: The study closed in December 1999 after an interim analysis demonstrated little likelihood of CIFU showing superiority to FU/LV within the stipulated hazard ratio. A total of 1,135 patients were registered. At least one grade 4 toxicity occurred in 39% of patients receiving FU/LV and 5% of patients receiving CIFU. However, almost twice as many patients receiving CIFU discontinued therapy early compared with those receiving FU/LV. The 5-year OS is 70% (95% CI, 66% to 74%) for FU/LV and 69% (95% CI, 64% to 73%) for CIFU. The corresponding 5-year disease-free survival (DFS) is 61% (95% CI, 56% to 65%) and 63% (95% CI, 59% to 68%), respectively. For all patients, 5-year OS is 83%, 74%, and 55%; 5-year DFS is 78%, 67%, and 47% for N0, N1, and N2-3, respectively. CONCLUSION: CIFU had less severe toxicity but did not improve DFS or OS in comparison with bolus FU/LV.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Levamisol/administración & dosificación , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Colorectal adenomas are the usual precursors to carcinoma in sporadic and hereditary colorectal cancers (CRC). METHODS: A total of 220 CRC patients (stages 0, I, and II) were randomized prospectively in a double-blind pilot study of calcium chemoprevention by using recurrent colorectal adenomas as a surrogate end point. This trial is still in progress, and we report the preliminary findings on adenoma recurrence rates. RESULTS: Synchronous adenomas were present in 60% of patients, and cancer confined in a polyp was present in 23% of patients. The overall cumulative adenoma recurrence rate was 31% (19% in the first year, 29% for 2 years, and 35% for 3 years). The recurrence rates were greater for patients with synchronous adenomas: 38% at 3 years (P =.01). Lower stage was associated with higher adenoma recurrence rates (P =.04). Factors including age, sex, site of primary cancer, and whether the cancer was confined to a polyp were not significantly associated with differences in adenoma recurrence rates. CONCLUSIONS: The substantial adenoma recurrence rate in patients resected of CRC justifies colonoscopic surveillance on a periodic basis. Patients with higher rates of adenoma recurrences, such as CRC with synchronous adenomas, are ideal subjects for chemoprevention trials.
Asunto(s)
Adenoma/patología , Neoplasias Colorrectales/patología , Adenoma/prevención & control , Adenoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carbonato de Calcio/uso terapéutico , Distribución de Chi-Cuadrado , Colonoscopía , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/cirugía , Método Doble Ciego , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias Primarias Múltiples , Proyectos Piloto , Estudios ProspectivosRESUMEN
Advanced follicular lymphoma is incurable with conventional chemotherapy and radiotherapy. The Southwest Oncology Group (SWOG) conducted a phase 2 trial (S9911) of a novel regimen consisting of 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy followed 4 to 8 weeks later by tositumomab/iodine I 131 tositumomab (anti-CD20 antibody) in 90 eligible patients with previously untreated, advanced stage follicular lymphoma. Treatment was well tolerated. Reversible myelosuppression was the main adverse event and was more severe during CHOP chemotherapy than following radioimmunotherapy. The overall response rate to the entire treatment regimen was 90%, including 67% complete remissions (CRs plus unconfirmed CRs [CRu's]) and 23% partial remissions (PRs). Twenty-seven (57%) of the 47 fully evaluable patients who achieved less than a CR with CHOP improved their remission status after tositumomab/iodine I 131 tositumomab. With a median follow-up of 2.3 years, the 2-year progression-free survival (PFS) was estimated to be 81%, with a 2-year overall survival of 97%. This study has established the feasibility, tolerability, and efficacy of this regimen for patients with advanced follicular lymphoma. This novel treatment appears promising compared with the SWOG's historical experience using CHOP alone and is currently being compared with CHOP plus rituximab in a randomized phase 3 trial (S0016).
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Linfoma Folicular/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Prednisona/administración & dosificación , Vincristina/administración & dosificación , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/efectos adversos , Doxorrubicina/efectos adversos , Femenino , Humanos , Radioisótopos de Yodo/administración & dosificación , Radioisótopos de Yodo/efectos adversos , Linfoma Folicular/mortalidad , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Defectos del Tubo Neural/inducido químicamente , Cooperación del Paciente , Prednisona/efectos adversos , Inducción de Remisión , Tasa de Supervivencia , Resultado del Tratamiento , Vincristina/efectos adversosRESUMEN
BACKGROUND: Adjuvant combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil plus vincristine and prednisone (CMFVP) was compared with single-agent L-phenylalanine mustard (L-PAM) for the treatment of patients with axillary lymph node positive primary breast carcinoma over 20-years of follow-up. METHODS: Four hundred forty-one women with axillary lymph node positive breast carcinoma were randomized to receive either combination chemotherapy with cyclophosphamide (60 mg/m(2) orally every day for 1 year), fluorouracil (300 mg/m(2) intravenously [IV] weekly for 1 year), methotrexate (15 mg/m(2) IV weekly for 1 year), vincristine (0.625 mg/m(2) IV for 10 weeks), prednisone (30 mg/m(2) orally on Days 1-14, 20 mg/m(2) on Days 15-28, and 10 mg/m(2) on Days 29-42), or single-agent chemotherapy with L-PAM (5 mg/m(2) orally every day for 5 days every 6 weeks for 2 years) after undergoing surgery. Patients were stratified according to menopausal status and number of positive lymph nodes (1-3 positive lymph nodes or > 3 positive lymph nodes). Seventy-seven patients were ineligible. RESULTS: The maximum follow-up is 24 years, with a median follow-up of 21.5 years. Disease free survival and overall survival were superior with CMFVP (two-sided log-rank test; P = 0.0008 and P = 0.007, respectively). For all patients, the estimated 20-year survival rate of patients who received CMFVP was 40% compared with 27% for patients who received L-PAM. There was a substantial survival benefit for CMFVP compared with L-PAM in the subsets of premenopausal patients and patients with four or more positive lymph nodes. The estimated 20-year survival rate for premenopausal women who received CMFVP was 49% compared with 33% for premenopausal women who received L-PAM. Among women with > or = 4 positive lymph nodes, the estimated survival rate for patients who received CMFVP was 31% compared with 15% for patients who received L-PAM. Both regimens were tolerated well. Toxicity was more severe and frequent among patients who received CMFVP. CONCLUSIONS: The authors conclude that, after 20 years of follow-up, adjuvant chemotherapy with CMFVP remains superior to L-PAM for the treatment of patients with lymph node positive breast carcinoma.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Fluorouracilo/uso terapéutico , Melfalán/uso terapéutico , Metotrexato/uso terapéutico , Prednisona/uso terapéutico , Vincristina/uso terapéutico , Adulto , Anciano , Antineoplásicos Alquilantes/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Axila , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/efectos adversos , Humanos , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Metástasis Linfática , Mastectomía Radical Modificada , Mastectomía Radical , Melfalán/efectos adversos , Menopausia , Metotrexato/efectos adversos , Persona de Mediana Edad , Prednisona/efectos adversos , Tasa de Supervivencia , Vincristina/efectos adversosRESUMEN
BACKGROUND: Prostate cancer is the most common malignancy in American men, and as many as 70% of those initially treated for localized disease will ultimately progress and be considered candidates to receive therapy for metastatic cancer [Fuks et al.: Int J Radiat Oncol Bio Phys 21:537-547, 1991; Chodak et al.: N Engl J Med 330:246-248, 1994]. Although most will respond initially to hormone manipulation, essentially all will fail and require additional therapy. No standard chemotherapy approach has been shown to prolong survival significantly, and new agents are desperately needed. Topotecan is a new topoisomerase-1 inhibitor whose early investigation suggested possible activity in hormone-refractory prostate cancer. METHODS: In this phase II trial, patients having failed one or two prior androgen ablative therapies were treated with 21-day continuous intravenous infusions of topotecan at a dose of 0.5 mg/m(2) per day every 28 days. RESULTS: Twenty-six eligible patients were entered on the study. There were no confirmed tumor responses. Median survival was 9 months. The most common toxicities were hematologic, with 8 of 24 assessable patients experiencing grade 4 toxicity. CONCLUSION: Topotecan infusions at this dose are ineffective in the management of hormone-refractory prostate cancer.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Topotecan/farmacología , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Resistencia a Antineoplásicos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Análisis de Supervivencia , Topotecan/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: It is increasingly important to have timely information about the economic impact of new cancer therapies in today's cost-conscious environment. Nearly 170 000 people are diagnosed with lung cancer annually in the United States. We performed an economic analysis alongside Southwest Oncology Group Trial S9509 to estimate the cost-effectiveness of cisplatin plus vinorelbine versus carboplatin plus paclitaxel for patients with advanced non-small-cell lung cancer. There were no statistically significant differences in survival or cancer-related quality of life between the treatment arms. METHODS: Use of both protocol and nonprotocol lung cancer-related health care was tracked for 24 months from the initiation of therapy. To determine expenditures, nationally standardized costs were applied to each type of health care service used, and these were summed over time. Lifetime expenditures and 95% confidence intervals (CIs) for each arm of the trial were calculated with the use of a multivariate regression technique that accounts for censoring. Student's t tests were used to compare the difference in costs between the arms. All statistical tests were two-sided. RESULTS: Cancer-related health care costs over the period of observation averaged 40,292 dollars (95% CI = 36,226 dollars to 44,359 dollars) for patients in the cisplatin plus vinorelbine arm versus 48,940 dollars (95% CI = 44,674 dollars to 53,208 dollars) for patients in the carboplatin plus paclitaxel arm (P =.004), with a mean difference of 8648 dollars (95% CI = 2634 dollars to 14,662 dollars). Protocol chemotherapy drugs and medical procedures costs were statistically significantly higher in the paclitaxel arm (P =.0003 and P<.0001, respectively), whereas protocol chemotherapy delivery costs were statistically significantly higher in the vinorelbine arm (P<.0001). There was no difference between the arms in costs for blood products, supportive care medications, nonprotocol-related inpatient or outpatient care, and nonprotocol chemotherapy. CONCLUSIONS: Treatment with carboplatin plus paclitaxel is substantially and statistically significantly more expensive than treatment with cisplatin plus vinorelbine. The majority of the cost difference is due to the additional cost of the protocol chemotherapy (approximately 12,000 dollars). Notable differences in costs of downstream health care were not apparent.