RESUMO
BACKGROUND: Tumor necrosis factor-alpha (TNFalpha)-based hyperthermic isolated limb perfusion (HILP) is routinely carried out at most oncological institutions in the treatment of locally advanced soft tissue limb sarcoma (STS), employing high TNFalpha dosages. After a phase I-II study, the SITILO (Italian Society of Integrated Locoregional Therapies in Oncology) centers began to employ the lower dose of 1 mg of TNFalpha. The aim of this paper is to report on the results obtained in 75 patients with limb-threatening STS treated with a low TNFalpha dose and doxorubicin (Dx). PATIENTS AND METHODS: HILP with TNFalpha (at a dosage of either
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doxorrubicina/administração & dosagem , Hipertermia Induzida , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Fator de Necrose Tumoral alfa/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia do Câncer por Perfusão Regional/métodos , Intervalo Livre de Doença , Extremidades/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perfusão , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: In isolated limb perfusion (ILP) with tumor necrosis factor-alpha (TNFalpha) and interferon (IFN)-gamma, pioneered by Lienard and Lejenne in 1988, TNFalpha was empirically employed at a dosage (3-4 mg) ten times higher than the systemic maximum tolerable dose (MTD). We previously conducted a phase I/II study in 20 patients with in-transit melanoma metastases, using a combination of melphalan and TNFalpha at dosages ranging from 0.5 to 3.3 mg. The dose of 1 mg of TNFalpha was identified as optimal in terms of both efficacy and toxicity. The aim of the present study was to describe our experience with 113 stage IIIA/IIIAB melanoma patients treated with a TNFalpha-based ILP and identify prognostic factors for response, locoregional control and survival. PATIENTS AND METHODS: Patients at stage IIIA-IIIAB (presence of in-transit metastases and/or regional node involvement) were considered eligible. The disease was bulky (>or=10 nodules
Assuntos
Melanoma/tratamento farmacológico , Melanoma/patologia , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Extremidades , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Melanoma/mortalidade , Melfalan/farmacologia , Pessoa de Meia-Idade , Metástase Neoplásica , Perfusão , Prognóstico , Resultado do TratamentoRESUMO
Quality can be considered to be a strategic element in the political process of planning and implementation of health and social care, resulting in a form of guarantee for the public through encouraging constructive competition between providers and reducing wasting and poor management. This should also be applied to managing loco-regional anesthesia. Competition is constant between treatments currently available together with a focus on quality and costs. This brings about strict controls on health care costs which should then be based on the evaluation of the results obtained in terms of health. It is obvious that costs for materials, time spent for an intervention, staff employed and structures required to carry it out are unavoidable. Quality is that treatment which maximises the patient's well-being following evaluation of the expected risks and benefits involved in the overall treatment. Acute pain is suffered by surgical patients either due to pre-existing disease, surgical intervention or due to a combination of both these situations. There is a high incidence of postoperative pain. In fact, more than 75% of postoperative patients report to have suffered moderate to severe pain. The same results have been reported in pediatrics and oncology: these results should always encourage the application of clinical quality, taking into consideration the costs involved when carrying out loco-regional anesthesia which aims at improving patient's outcome when undergoing surgical intervention.
Assuntos
Anestesia Local/economia , Anestesia Local/normas , Humanos , Garantia da Qualidade dos Cuidados de SaúdeRESUMO
Hyperthermic Limb Perfusion (HILP) with Tumor Necrosis Factor alpha (TNFalpha) and interferon gamma (IFNgamma) was pioneered by Liénard and Lejeune in 1988. TNFalpha was empirically employed at a dosage of 3-4 mg that is ten times the systemic maximum tolerated dose (MTD). Sixteen years after its first clinical application more than 300 patients have been treated and some clarifications can be made regarding three major questions: the real role of IFNgamma, the TNFalpha dose and eligibility criteria for patient selection. A randomized phase II study has demonstrated that IFNgamma does not increase significantly the efficacy but does increase side-effects. Experimental and clinical results seem to indicate that patients with bulky melanoma disease can really benefit from TNFalpha HILP carried out with only 1 mg.
Assuntos
Quimioterapia do Câncer por Perfusão Regional/métodos , Hipertermia Induzida , Melanoma/tratamento farmacológico , Fator de Necrose Tumoral alfa/administração & dosagem , Animais , Extremidades , Humanos , Interferon gama/farmacologia , Dose Máxima Tolerável , RecidivaRESUMO
Liposome-containing doxorubicin has been employed in the treatment of advanced soft tissue limb sarcoma during hyperthermic perfusion. A phase I-II study was carried out starting with a standard dose of 10 mg//L of limb volume, the dosage was escalated with 2 mg for each triplet of patients. The maximum tolerable (MTD) dose was established as the amount able to cause a grade IV limb reaction at least in two out of three patients, the temperature level remained unchanged (41.5 degrees C). The grade of limb reaction ranged between I-II (mild edema and erythema). Only in two patients treated with 18 mg/L of limb volume was a grade IV limb reaction observed, therefore MTD at a temperature of 41.5 degrees C is 16 mg. A good tumor response was observed in 29% of the patients, partial response in 71%. The tumor shrinkage after perfusion permitted conservative surgery in 91% of the cases.
Assuntos
Quimioterapia do Câncer por Perfusão Regional/métodos , Doxorrubicina/administração & dosagem , Hipertermia Induzida , Sarcoma/tratamento farmacológico , Adulto , Idoso , Extremidades , Feminino , Humanos , Lipossomos , Masculino , Pessoa de Meia-IdadeRESUMO
Hyperthermic antiblastic perfusion (HAP) has been proven to be an effective treatment of loco-regional spreading limb melanoma. The mean complete response (CR) rate obtained is 54%, with an objective responses (OR) rate ranging between 70% and 100%. Recently, Tumor Necrosis Factor (TNFalpha) has been employed at high dosages (3-4 mg) in association to Melphalan and hyperthermia. This trimodality combination increased the percentage of CR (70%-90%), but systemic toxicity was also reported due to high TNF doses. A phase I - II study was undertaken in order to assess the MTD of TNFalpha in association to true hyperthermia (41.5 degrees C) and Melphalan. Twenty patients affected with stages IIIA (9 patients), IIIAB (10 patients), and IV (1 patient) were enrolled in this study. The trimodality treatment did not increase the local and systemic toxicity. CR was observed in 70% of the patients, PR in 20% with on OR rate of 90%. These figures are overlapping those obtained with high TNF dosages. No correlation was observed between tumor responses and TNF doses. Taking into account that 70% of our patients have been treated with TNF dosages between 0.5 mg on 1.6 mg, we conclude that 1 mg is the best dosage to be applied during HAP. Patients with bulky tumor are the best candidate to TNF perfusion, because no differences have been observed in terms of CR in patients with low tumor burden treated with TNF-Melphalan-hyperthermia or Melphalan-hyperthermia.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional , Hipertermia Induzida , Melanoma/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Terapia Combinada , Relação Dose-Resposta a Droga , Extremidades/patologia , Feminino , Humanos , Hipertermia Induzida/efeitos adversos , Masculino , Dose Máxima Tolerável , Melanoma/mortalidade , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Análise de Sobrevida , Fator de Necrose Tumoral alfa/administração & dosagem , Fator de Necrose Tumoral alfa/efeitos adversosRESUMO
AIMS: Some low-grade malignant tumours arising in the abdomen tend to remain loco-regionally confined to peritoneal surfaces, without systemic dissemination. In these cases complete surgical tumour cytoreduction followed by intra- or post-operative regional chemotherapy has curative potential. The aim of this study was to evaluate the outcome for patients treated in this way. METHODS: Peritonectomy was performed, involving the complete removal of all the visceral and parietal peritoneum involved by disease. After peritonectomy, hyperthermic antiblastic perfusion was carried out throughout the abdominopelvic cavity for 90 min, at a temperature of 41.5-42.5 degrees C, with mitomycin C (3.3 mg/m2/l) and cisplatin (25 mg/m2/l) (for appendicular or colorectal primaries), or cisplatin alone (for ovarian primaries). Alternatively, the immediate post-operative regional chemotherapy was performed with 5-fluorouracil (13.5 mg/kg) and Lederfolin (125 mg/m2) (for colonic or appendicular tumours) or cisplatin (25 mg/m2) (for ovarian tumours), each day for 5 days. RESULTS: Thirty-five patients affected by extensive peritoneal carcinomatosis were submitted to peritonectomy, with no residual macroscopic disease in all cases except three. Twenty-six patients were able to undergo the combined treatment involving loco-regional chemotherapy. Complications were observed in 54% of the patients and led to death in four of them. At a mean follow-up of 17 months overall 2-year survival was 55.2%, with a median survival of 26 months. CONCLUSIONS: After a learning curve of 18 months the feasibility of the integrated treatment increased to more than 90%, while mortality decreased dramatically. The curative potential of the combined therapeutic approach seems high in selected patients with peritoneal carcinomatosis not responding to systemic chemotherapy. Careful selection of patients can minimize the surgical risk, but the treatment should currently be reserved for clinical trials.