RESUMO
BACKGROUND: A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial. PATIENTS AND METHODS: Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks. RESULTS: Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively. CONCLUSION: This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.
Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/administração & dosagem , Antígeno CA-19-9/sangue , Desoxicitidina/análogos & derivados , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores Farmacológicos/sangue , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Resultado do Tratamento , GencitabinaRESUMO
Cimetidine has demonstrated a survival benefit in a randomized trial as adjuvant therapy for gastric cancer. We have demonstrated expression of histamine receptors on colon cancer cell lines and inhibition of their growth with cimetidine. Cimetidine also activates suppressor T cells and stimulates cell-mediated immunity. We therefore performed a randomized controlled clinical trial to determine the effect of cimetidine 400 mg given twice daily in conjunction with chemotherapy vs chemotherapy alone. Thirty-eight patients were randomized and 35 patients were eligible for further analysis. Both groups were well matched for pre-treatment characteristics. There was no difference in overall response. There was, however, a significantly increased rate of CEA response in the cimetidine group. Four of 11 patients (36%) in the cimetidine group had a CEA response compared to none of eight in the control. Meaningful comparisons of overall survival cannot yet be made. This study demonstrates that cimetidine has encouraging activity in increasing CEA response in patients with metastatic colorectal cancer treated with chemotherapy. This observation needs to be extended in a larger randomized study, which is currently underway.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/sangue , Cimetidina/administração & dosagem , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: The present study reviews the nature of upper gastrointestinal complications of hepatic arterial chemoperfusion at a tertiary referral centre for the treatment of hepatic malignancy. METHODS: The patients involved in the present study all had major upper gastrointestinal (GI) haemorrhage and were undergoing hepatic arterial chemoperfusion. RESULTS: Eight patients had major upper GI haemorrhage. Three of these patients were not referred for surgical management, and all three patients died. The five patients who were admitted or transferred to our unit and who underwent surgery all survived. CONCLUSIONS: These complications are probably caused by extravasation of 5-fluorouracil (5-FU) following thrombosis of the gastroduodenal artery. The resulting cavity may perforate into the hepatic artery, portal vein, duodenum or biliary tree. Surgeons and oncologists should be aware of these complications. If upper abdominal pain occurs, chemoperfusion should cease immediately and an urgent investigation, which may include catheter angiography, gastroscopy and computed tomography (CT) scanning, should be carried out to exclude an hepatic artery pseudo-aneurysm.
Assuntos
Fluoruracila/efeitos adversos , Hemorragia Gastrointestinal/etiologia , Infusões Intra-Arteriais/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Úlcera Duodenal/induzido quimicamente , Úlcera Duodenal/complicações , Feminino , Fluoruracila/administração & dosagem , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/cirurgia , Artéria Hepática , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica/etiologiaRESUMO
BACKGROUND: The present paper addressed the issue of whether pretreatment with intravenous (i.v.) chemotherapy affects response rate or survival in patients receiving hepatic artery chemotherapy (HAC). METHODS: Case note reviews of 164 patients treated in a teaching hospital from June 1990 to July 1996 were carried out. RESULTS: The response rate and carcino-embryonic antigen (CEA) fall in the two groups was almost identical. There was a nonsignificant survival advantage in the non-pretreatment group. CONCLUSIONS: Previous administration of i.v. chemotherapy did not affect the CEA response of patients receiving HAC.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/patologia , Fluoruracila/administração & dosagem , Artéria Hepática/efeitos dos fármacos , Infusões Intra-Arteriais , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Antídotos/administração & dosagem , Antígeno Carcinoembrionário/metabolismo , Neoplasias Colorretais/mortalidade , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Taxa de SobrevidaRESUMO
Between 1978 and 1985, 247 patients with primary breast cancer have been treated with breast conserving surgery and external beam radiotherapy. Median follow-up is 3 years and 9 months. Actuarial 5-year disease-free survival for the whole group is 72%; 16 patients (6.8%) have relapsed in the breast to date. Of these, 6 (38%) have died from breast cancer. Patients who have experienced a local recurrence have significantly worse survival than those who remain locally recurrence-free (p less than 0.001). Complication data are presented and shown to be almost entirely mild to moderate and in the range 1-19%. This series shows the breast conserving approach to be effective and at least equivalent to breast ablative procedures in early follow-up.
Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Mastectomia Segmentar , Recidiva Local de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Neoplasias da Mama/mortalidade , Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/radioterapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Between 1978 and 1985, 247 breast cancer patients were treated with breast conserving surgery and radiotherapy. One hundred and twenty of these patients form the basis of this report, having replied to an 11-point structured questionnaire evaluating breast appearance and breast, shoulder and arm function. Good to perfect cosmetic, functional and overall scores are shown to be in the range 61-89%. The extent of primary surgery and axillary irradiation are the major factors affecting the cosmetic appearance. Other problems with cosmetic and functional assessment from subjective and objective view points are also discussed.
Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mama/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braço/fisiologia , Mama/patologia , Neoplasias da Mama/psicologia , Terapia Combinada , Estética , Feminino , Humanos , Excisão de Linfonodo , Mastectomia/métodos , Mastectomia Segmentar , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Regional chemotherapy has achieved high response rates in hepatic metastases from colorectal cancer and has been shown to improve survival significantly. The present paper reports the use of pre-operative regional therapy to establish marker response as a means of selection of patients for surgery. Fourteen patients underwent radiologically placed hepatic artery catheter (HAC) for chemotherapy. In the 11 patients with carcino-embryonic antigen (CEA) fall the patient proceeded to open surgical placement of HAC. The predictive effect of CEA fall following radiological HAC was good. Non-responding patients are clearly spared the discomfort and inconvenience and costs of an unnecessary operation.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Cateterismo Periférico , Neoplasias Colorretais/patologia , Fluoruracila/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Adulto , Idoso , Antígeno Carcinoembrionário/análise , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Serum carcinoembryonic antigen (CEA) levels in 33 Australian patients with hepatic metastases from colorectal cancer were measured before and after treatment with hepatic cryotherapy and intra-arterial chemotherapy. Pre-operative and monthly postoperative CEA measurements were made and the lowest postoperative reading was recorded as a percentage fall from the pre-operative level. There was a highly significant association between the maximum percentage fall in CEA and survival. A 50% increase in the maximum percentage fall in CEA level was associated with one-tenth the risk of death (95% CI RR 0.03 to 0.32, Cox regression). It is estimated that an increase in the maximum percentage fall in CEA of 50% from 25 to 75% was associated with an increase in the median survival from 240 days to over 2 years.
Assuntos
Antígeno Carcinoembrionário/sangue , Neoplasias do Colo/patologia , Crioterapia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Antineoplásicos/uso terapêutico , Neoplasias do Colo/mortalidade , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Análise de SobrevidaRESUMO
Thirty-eight patients with unresectable multiple liver metastases from colorectal carcinoma were treated with either hepatic artery chemotherapy (HAC) and cryotherapy (n = 27) or cryotherapy alone (n = 11). Follow-up survival data were summarized using Cox regression. Allowing for the effect of the pathology of the primary tumor and the preoperative carcinoembryonic antigen (CEA) level, those patients who did not receive HAC after cytoreduction were three times as likely to die as those given HAC (RR 3.3, 95%; CI 1.2-9.3). The estimated median survival of patients treated with cryotherapy alone was 245 days, whereas for those given more than 3 months of HAC plus cytoreduction therapy it was 570 days. It is recommended that all patients who receive cryotherapy for multiple liver metastases from colorectal rectal carcinoma be given subsequent hepatic artery chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Criocirurgia , Infusões Intra-Arteriais , Neoplasias Hepáticas/secundário , Adulto , Idoso , Quimioterapia Adjuvante , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de SobrevidaRESUMO
Twenty-two patients with colorectal cancer and synchronous unresectable hepatic metastases were treated by resection the primary tumour with concurrent insertion of an Infusaid infusaport system for regional chemoperfusion (hepatic arterial 20, portal venous 2). Four patients in addition had cryotherapy the liver metastases. Morbidity from the synchronous procedures was minimal. Median survival was 10 months. Four patients with poorly-differentiated tumours had a poor response, with a median survival of 3.75 months.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias Colorretais/cirurgia , Criocirurgia , Fluoruracila/administração & dosagem , Neoplasias Hepáticas/secundário , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Taxa de SobrevidaRESUMO
OBJECTIVES: (i) To assess the efficacy and tolerability of tropisetron when used for acute and delayed cisplatin-induced emesis. (ii) To investigate whether dexamethasone added to tropisetron improves the control of emesis for patients who do not achieve a complete response to tropisetron alone. (iii) To assess sex of the patient and alcohol intake as prognostic factors for nausea and vomiting. DESIGN: A prospective open label phase II trial over one or two cycles of chemotherapy. Data collection was based on observed response and patients' self-reporting. SETTING: Twenty Australian tertiary care hospitals in 1994. PATIENTS: 102 male and female patients from 18 to 75 years with histologically confirmed malignancy receiving their first chemotherapy containing > or = 50 mg/m2 cisplatin. INTERVENTION: In Cycle 1 tropisetron 5 mg was given intravenously before chemotherapy on Day 1, then 5 mg orally before breakfast on Days 2 to 6. In Cycle 2, dexamethasone 20 mg intravenously on Day 1, then 8 mg orally on Days 2 to 6 could be added to tropisetron if a complete antiemetic response had not been achieved in Cycle 1. MAIN OUTCOME MEASURES: Number of vomiting episodes and severity of nausea for 6 days after chemotherapy; severity of side effects; patient satisfaction with chemotherapy treatment; oestradiol levels in women; and past alcohol consumption in men and women. RESULTS: (i) The complete response rate (CR) for acute emesis in Cycle 1 was 64% (95% confidence interval [CI], 54%-72%), with 84% (95% CI, 76%-90%) having < or = 2 vomits. The CR for delayed emesis was 24% (95% CI, 17%-32%). The CR for acute nausea was 56% (95% CI, 47%-66%), with 97% (95% CI, 91%-99%) having < or = 2 nausea episodes. The CR for delayed nausea was 21% (95% CI, 14%-30%). Seventy-one patients received Cycle 2. The main side effects were headache (20 patients) and constipation (16 patients). The control of acute emesis was rated as "good" or "very good" by 68% of investigators; 85% rated the tolerability of treatment as "good" or "very good". Treatment was rated as "very satisfactory" or "satisfactory" by 52% of patients. (ii) The CR for acute emesis with dexamethasone added was 78% (95% CI, 64%-88%). (iii) Women with lower oestradiol levels had better control of emesis, although this difference was not statistically significant. Chronic alcohol intake and binge drinking were strongly associated with a complete acute antiemetic response. CONCLUSIONS: Tropisetron was effective for acute cisplatin-induced emesis; adding dexamethasone enhanced this response. Both single and combined therapy had less effect on delayed emesis. The impact of alcohol on control of emesis is a chronic rather than acute phenomenon which requires prospective testing.