RESUMO
PURPOSE: To compare fotemustine and dacarbazine (DTIC) in terms of overall response rate (ORR) as primary end-point and overall survival, duration of responses, time to progression, time to occurrence of brain metastases (BM), and to assess safety and quality of life in patients with disseminated cutaneous melanoma. PATIENTS AND METHODS: Patients received either intravenous fotemustine 100 mg/m2 weekly for 3 weeks or DTIC 250 mg/m2/d for 5 consecutive days every 4 weeks (two cycles). Nonprogressive patients received a maintenance treatment every 4 weeks (fotemustine 100 mg/m2 or DTIC 250 mg/m2 for 5 days). RESULTS: Two hundred twenty-nine patients were randomly assigned to fotemustine or DTIC arms. The best ORR was higher in the fotemustine arm than in the DTIC arm in the intent-to-treat population (n=229; 15.2% v 6.8%; P=.043) and in full analysis set (n=221) (15.5% v 7.2%; P=.053). Similar median durations of responses (5.8 months with fotemustine v 6.9 months with DTIC) and time to progression (1.8 v 1.9 months, respectively) were observed. In patients without BM at inclusion, the median time to BM was 22.7 months with fotemustine versus 7.2 months with DTIC (P=.059). Median survival was 7.3 months with fotemustine versus 5.6 months with DTIC (P=.067). The main toxicity was grade 3 to 4 neutropenia (51% with fotemustine v 5% with DTIC) and thrombocytopenia (43% v 6%, respectively). No significant difference was noted for quality of life between arms. CONCLUSION: ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.
Assuntos
Antineoplásicos/uso terapêutico , Dacarbazina/uso terapêutico , Melanoma/tratamento farmacológico , Compostos de Nitrosoureia/uso terapêutico , Compostos Organofosforados/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/secundário , Dacarbazina/efeitos adversos , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Compostos de Nitrosoureia/efeitos adversos , Compostos Organofosforados/efeitos adversos , Qualidade de Vida , Neoplasias Cutâneas/patologia , Estatísticas não Paramétricas , Análise de SobrevidaRESUMO
The purpose of this randomized trial was to evaluate the efficacy of combination chemoimmunotherapy compared with chemotherapy alone. A total of 124 patients were randomized to receive intravenous cisplatin (35 mg m(-2), days 1-3), carmustine (150 mg m(-2), day 1, cycles 1 and 3 only), dacarbacine (220 mg m(-2), days 1-3) and oral tamoxifen (20 mg m(-2), daily) in combination with (n=64) or without (n=60) sequential subcutaneous IL-2 and IFN-alpha. In those patients who received sequential immunotherapy, each cycle of chemotherapy was followed by outpatient s.c. IL-2 (10 x 10(6) IU m(-2), days 3-5, week 4; 5 x 10(6) IU m(-2), days 1, 3, 5, week 5) and s.c. IFN-alpha (5 x 10(6) IU m(-2), day 1, week 4; days 1, 3, 5, week 5). The overall response rate of patients treated with the combination of chemotherapy and IL-2/IFN-alpha was 34.3% with seven complete responses (10.9%) and 15 partial responses (23.4%). In patients treated with chemotherapy, only, the overall response rate was 29.9% with eight complete responses (13.3%) and 10 partial responses (16.6%). There was no significant difference in median progression free survival (0 months vs 4 months) and in median overall survival (12 months vs 13 months) for combined chemoimmunotherapy and for chemotherapy, respectively.
Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interferon-alfa/farmacologia , Interleucina-2/farmacologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Antineoplásicos/administração & dosagem , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Cutâneas/patologia , Tamoxifeno/administração & dosagem , Resultado do TratamentoRESUMO
Abstract. In this communication, we will present a very rare case of the coexistence of non-Hodgkin's lymphoma (NHL; low malignant lymphocytic lymphoma of the B-cell type) and a non-small-cell lung carcinoma (NSCLC). A patient with a 15-year history of NHL developed a generalized relapse of the lymphoma with an additional tumor mass in the left lower lobe of the lung. Bronchoscopy showed the evidence of the NHL. Due to non-responding chemotherapy on the lung tumor, the coexistence of a second malignancy was histologically proved in a second bronchoscopy. Resection of the lung tumor with complex lobectomy and lymphadenectomy was performed. After that, chemotherapy with four cycles of carboplatin supplemented with taxol was induced. The patient was discharged from the hospital with a stable remission of both tumor diseases. Restaging after six months showed no evidence of a tumor relapse. This is a very rare case of the coexistence of NHL and NSCLC; we will discuss the difficulty of diagnostic and treatment of both tumor diseases.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfoma não Hodgkin , Segunda Neoplasia Primária , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Broncoscopia , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Masculino , Segunda Neoplasia Primária/diagnóstico por imagem , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Paclitaxel/administração & dosagem , RadiografiaRESUMO
The prognosis of stage IV melanoma is unfavourable compared to the curative surgical results in early stage. The median survival amounts to 8-10 months and only 1-2% of the patients will not relapse. Dacarbazine remains the reference standard treatment for metastatic melanoma. The modest activity of chemotherapy in stage IV has prompted investigators to consider combinations of multiagent chemotherapy, immunotherapy and biochemotherapy. Promising treatment options are melanoma vaccines to obtain an efficient immunoresponse, the combination of chemotherapy with Interleukin (IL)-2 and Interferon alfa (IFN-alpha) as a way of improving response rates and survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia , Melanoma/secundário , Neoplasias Cutâneas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Ensaios Clínicos como Assunto , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Humanos , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Interleucina-2/efeitos adversos , Células Matadoras Ativadas por Linfocina/transplante , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Melanoma/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Taxa de SobrevidaRESUMO
Expression of mutant p53 detected by immunohistochemistry has been described in human malignant melanoma, but there are few reports of molecular analyses. To investigate the genetic basis for p53 expression in malignant melanoma, we examined 58 primary tumors and 5 cutaneous metastases. The entire coding sequence of the p53 gene was screened by single-strand conformation polymorphism analysis and direct genomic sequencing of polymerase chain reaction products. p53 and mdm-2 expression were studied by immunohistochemistry. Two p53 gene mutations could be found in 1/63 samples examined, both having occurred in the same specimen from a patient with a nodular melanoma. p53 and mdm-2 expression were found immunohistochemically to increase with tumor progression both in frequency and in the mean proportion of positive cells, with the same cases staining positively for both antibodies. Our results suggest that a) p53 gene mutations are a rare event in human melanoma; b) accumulation and thus immunohistochemically detectable expression of p53 may result from posttranslational mechanisms affecting the p53 gene product; and c) p53 and mdm-2 are more important in late events in melanoma carcinogenesis.
Assuntos
Genes p53 , Melanoma/genética , Mutação , Proteínas Nucleares , Proteínas Proto-Oncogênicas/genética , Neoplasias Cutâneas/genética , Sequência de Bases , Humanos , Imuno-Histoquímica , Melanoma/metabolismo , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas c-mdm2 , Neoplasias Cutâneas/metabolismo , Proteína Supressora de Tumor p53/biossínteseRESUMO
In order to evaluate the behaviour of N-(2-diethylaminoethyl)-4-[123I]iodobenzamide in malignant melanotic disease, we synthesized the bromo compound in a simple one-step reaction. Labelling was performed by non-isotopic bromine-iodine-123 exchange in radiochemical yields up to 60%. By means of isocratic high-performance liquid chromatography, the iodinated product could be isolated with high apparent specific activity. First clinical studies in patients with malignant melanoma using N-(2-diethylaminoethyl)-4-[123I]iodobenzamide showed moderate uptake of the tracer in the tumour and the suspected metastases in all patients. Most of the lesions were detectable with technetium-99m-diethylene triamine penta-acetic acid (DTPA) scintigraphy too, but we were able to detect additional, previously unidentified metastases with benzamide scintigraphy. This changed the therapeutic procedure in two of the five cases investigated so far.
Assuntos
Benzamidas , Radioisótopos do Iodo , Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Idoso , Cromatografia Líquida de Alta Pressão , Meios de Contraste , Feminino , Humanos , Marcação por Isótopo , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Radioimunodetecção , Pentetato de Tecnécio Tc 99mRESUMO
Three double-blind, dose-ranging studies, involving 996 chemotherapy-naive patients, were conducted to determine the optimal prophylactic dose of intravenous (i.v.) granisetron for prevention of cytotoxic-induced emesis. The antiemetic efficacy of prophylactic i.v. granisetron doses ranging from 2-40 micrograms/kg (study 1) and 40-160 micrograms/kg (study 2) were examined in patients receiving high-dose cisplatin regimens. In study 3, i.v. doses of 40 and 160 micrograms/kg were compared in patients receiving other emetogenic cytotoxic therapies. In study 1, 67.9% (36/53) of patients were complete responders at 24 h following the 40 micrograms/kg dose compared with 61.5% (32/52) and 30.8% (16/52) in the 10 and 2 micrograms/kg groups, respectively (40 vs. 2 micrograms/kg; P less than 0.001). There were no significant differences between doses of 40 and 160 micrograms/kg in any efficacy parameter in Studies 2 and 3. Granisetron was well tolerated across the dose range examined and no dose-related toxicity was observed. In conclusion, a single 40 micrograms/kg prophylactic dose provides optimal control of cytotoxic-induced nausea and vomiting. A simple 3 mg single-dose i.v. regimen (equivalent to 40 micrograms/kg in a 75 kg person) is recommended for prevention of acute emesis associated with all cytotoxic regimens.