RESUMEN
BACKGROUND: Src inhibitors sensitise melanoma cells to chemotherapy in preclinical models. The combination of dasatinib and dacarbazine was tested in a phase I trial in melanoma. METHODS: Patients had ECOG performance status 0-2 and normal organ function. Dacarbazine was administered on day 1 and dasatinib on day 2 through 19 of each 21-day cycle. Both were escalated from 50 mg b.i.d. of dasatinib and 800 mg m(-2) of dacarbazine. Available pre-treatment biopsies were sequenced for BRAF, NRAS, and C-Kit mutations. RESULTS: Dose-limiting toxicity was reached at dasatinib 70 mg b.i.d./dacarbazine 1000 mg m(-2), and was predominantly haematological. In 29 patients receiving dasatinib 70 mg b.i.d., the objective response rate (ORR) was 13.8%, the clinical benefit rate (ORR+SD) was 72.4%, the 6-month progression-free survival (PFS) was 20.7%, and the 12-month overall survival (OS) was 34.5%. Two out of three patients who were wild type for BRAF, NRAS, and c-KIT mutations had confirmed partial responses, and one had a minor response. CONCLUSION: The recommended phase II dose is dasatinib 70 mg b.i.d with dacarbazine 800 mg m(-2). PFS and OS data for dasatinib at 70 mg b.i.d. with dacarbazine compared favourably with historical controls. Preliminary data support evaluating tumour mutation status further as a biomarker of response.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Metástasis de la Neoplasia , Familia-src Quinasas/antagonistas & inhibidores , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dacarbazina/efectos adversos , Dasatinib , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Pirimidinas/efectos adversos , Análisis de Supervivencia , Tiazoles/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Docosahexaenoic acid-paclitaxel (DHA-paclitaxel, Taxoprexin(®)) is made by covalently conjugating the essential fatty acid DHA to the paclitaxel molecule. Preclinical studies of DHA-paclitaxel have demonstrated increased activity relative to paclitaxel and the potential for an improved therapeutic ratio. In the present study, the efficacy and toxicity profiles of DHA-paclitaxel were compared with those of dacarbazine. METHODS: In this study, 393 chemonaive patients with metastatic melanoma were randomly assigned to receive either DHA-paclitaxel at a starting dose of 900 mg/m(2) IV on day 1 every 3 weeks or dacarbazine at a starting dose of 1000 mg/m(2) IV on day 1 every 3 weeks. The primary end point of the study was the comparison of overall survival (OS). RESULTS: No significant difference in OS was noted between patients in the DHA-paclitaxel and dacarbazine arms. Similarly, there were no significant differences in response rate, duration of response, time to progression, and time to treatment failure between the two drugs. Safety results of the two drugs were as predicted from prior studies. Myelosuppression was more common with DHA-paclitaxel. CONCLUSIONS: DHA-paclitaxel was not superior to dacarbazine. We conclude that further studies with the drug on an every 3-week schedule in melanoma are not warranted.
Asunto(s)
Dacarbazina/uso terapéutico , Melanoma/tratamiento farmacológico , Paclitaxel/análogos & derivados , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dacarbazina/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Paclitaxel/efectos adversos , Paclitaxel/uso terapéuticoRESUMEN
PURPOSE: High-dose pegylated interferon α-2b (peginterferon α-2b) significantly decreased disease recurrence in patients with resected stage III melanoma in a clinical study. We investigated the pharmacokinetics (PK) and safety of high-dose peginterferon α-2b in patients with high-risk melanoma. METHODS: For PK analysis, 32 patients received peginterferon α-2b 6 µg/(kg week) subcutaneously for 8 weeks (induction) then 3 µg/(kg week) for 4 weeks (maintenance). PK profiles were determined at weeks 1, 8, and 12. Exposure-response relationships between peginterferon α-2b and absolute neutrophil count (ANC) and alanine aminotransferase (ALT) level were also studied. RESULTS: Peginterferon α-2b was well-absorbed following SC administration, with a median T (max) of 24 h. Mean half-life estimates ranged from 43 to 51 h. The accumulation factor was 1.69 after induction therapy. PK parameters showed moderate interpatient variability. PK profiles were described by a one-compartmental model with first-order absorption and first-order elimination. Toxicity was profiled and was acceptable; observed side effects were similar to those previously described. Dose reduction produced proportional decreases in exposure and predictable effects on ANC in an Imax model; however, a PK/pharmacodynamic (PK/PD) relationship between peginterferon α-2b and ALT could not be established with high precision. CONCLUSIONS: Peginterferon α-2b was well-absorbed and sustained exposure to peginterferon α-2b was achieved with the doses tested. These data confirm and extend previous PK observations of peginterferon α-2b in melanoma and solid tumors. Our PK/PD model of exposure and ANC effect provides useful information for prediction of peginterferon α-2b-related hematologic toxicity.
Asunto(s)
Interferón-alfa/farmacología , Melanoma/tratamiento farmacológico , Modelos Biológicos , Polietilenglicoles/farmacología , Adulto , Anciano , Quimioterapia Adyuvante/métodos , Terapia Combinada , Relación Dosis-Respuesta a Droga , Femenino , Semivida , Humanos , Inyecciones Subcutáneas , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/farmacocinética , Masculino , Melanoma/patología , Melanoma/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Polietilenglicoles/administración & dosificación , Polietilenglicoles/farmacocinética , Estudios Prospectivos , Proteínas Recombinantes , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Sagopilone is a novel fully synthetic epothilone with promising preclinical activity and a favourable toxicity profile in phase I testing. METHODS: A phase II pharmacokinetic and efficacy trial was conducted in patients with metastatic melanoma. Patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate haematological, and organ function, with up to 2 previous chemotherapy and any previous immunotherapy regimens. Sagopilone, 16 mg m⻲, was administered intravenously over 3 h every 21 days until progression or unacceptable toxicity. RESULTS: Thirty-five patients were treated. Sagopilone showed multi-exponential kinetics with a mean terminal half-life of 64 h and a volume of distribution of 4361 l m⻲ indicating extensive tissue/tubulin binding. Only grade 2 or lower toxicity was observed: these included sensory neuropathy (66%), leukopenia (46%), fatigue (34%), and neutropenia (31%). The objective response rate was 11.4% (one confirmed complete response, two confirmed partial responses, and one unconfirmed partial response). Stable disease for at least 12 weeks was seen in an additional eight patients (clinical benefit rate 36.4%). CONCLUSION: Sagopilone was well tolerated with mild haematological toxicity and sensory neuropathy. Unlike other epothilones, it shows activity against melanoma even in pretreated patients. Further clinical testing is warranted.
Asunto(s)
Benzotiazoles/toxicidad , Benzotiazoles/uso terapéutico , Epotilonas/toxicidad , Epotilonas/uso terapéutico , Melanoma/tratamiento farmacológico , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Antineoplásicos/toxicidad , Benzotiazoles/farmacocinética , Progresión de la Enfermedad , Epotilonas/farmacocinética , Femenino , Semivida , Humanos , Masculino , Melanoma/patología , Melanoma/radioterapia , Melanoma/cirugía , Metástasis de la Neoplasia , Estadificación de Neoplasias , Estudios Prospectivos , Medición de Riesgo , Resultado del Tratamiento , Moduladores de Tubulina/uso terapéutico , Moduladores de Tubulina/toxicidadRESUMEN
PURPOSE: To determine dose-response effects and the activity of paclitaxel combined with cisplatin in patients with incurable squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Two hundred ten patients with locally advanced, recurrent, or metastatic disease were randomly placed in either Arm A, paclitaxel 200 mg/m(2) (24-hour infusion) + cisplatin 75mg/m(2) + granulocyte colony-stimulating factor, or Arm B, paclitaxel 135 mg/m(2) (24-hour infusion) + cisplatin 75 mg/m(2). Cycles were repeated every 3 weeks until progression or a total of 12 cycles for complete responses. Primary outcomes were event-free and overall survival. RESULTS: No significant differences in outcomes were observed between the high- and low-dose paclitaxel regimens. The estimated median survival was 7.3 months (95% confidence interval, 6.0 to 8.6). The 1-year survival rate was 29%, and event-free survival was 4.0 months. The objective response rate (complete response plus partial response) was 35% for the high-dose patients and 36% for the low-dose patients. Myelosuppression was the most frequent toxicity: grade 3 or 4 granulocytopenia, 70% of patients in Arm A and 78% in Arm B; febrile neutropenia, 27% of patients in Arm A and 39% in Arm B. Grade 5 toxicities occurred in 22 patients (10.5%). Treatment was terminated early in 31% because of excessive toxicity or patient refusal. CONCLUSION: This phase III multicenter trial showed (1) no advantage for high-dose paclitaxel and (2) excessive hematologic toxicity associated with both regimens. Therefore, neither of the paclitaxel regimens evaluated in this trial can be recommended.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Paclitaxel/administración & dosificación , Adulto , Anciano , Agranulocitosis/inducido químicamente , Carcinoma de Células Escamosas/mortalidad , Esquema de Medicación , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamenteAsunto(s)
Carcinoma de Células de Merkel/patología , Carcinoma de Células de Merkel/terapia , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Anciano , Biopsia con Aguja/normas , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/mortalidad , Terapia Combinada , Femenino , Guías como Asunto , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/mortalidad , Tasa de SupervivenciaRESUMEN
Chemotherapy has been integrated into the initial treatment of patients with locally advanced squamous cell cancer of the head and neck to improve locoregional control and survival. Two strategies for improving these outcomes are the use of new, potentially more effective drugs either with concurrent radiotherapy or as induction regimens. Because of its inherent activity against squamous cell cancer of the head and neck and its radiation-sensitizing properties, paclitaxel may be a valuable agent in the treatment of this patient population. We describe the preliminary results of two trials that evaluated the combination of paclitaxel and cisplatin in patients with locally advanced disease: a phase I trial of weekly paclitaxel and cisplatin with concurrent postoperative radiation therapy in patients with high-risk disease and a phase I/II trial of paclitaxel as a 96-hour infusion in combination with cisplatin as induction therapy. These studies identified tolerable doses of paclitaxel and cisplatin administered in these settings, with apparent clinical activity. These trials formed the basis for subsequent evaluation of induction paclitaxel and cisplatin followed by definitive radiotherapy and concurrent weekly paclitaxel and cisplatin plus radiotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Proyectos Piloto , Resultado del TratamientoRESUMEN
CONTEXT: For most solid tumors, the metastatic status of regional lymph nodes is the strongest predictor of relapse and survival. However, routine pathological examination of lymph nodes may underestimate the number of patients with melanoma who have nodal metastases. OBJECTIVE: To determine the clinical significance of a highly sensitive molecular assay for occult nodal metastases for the staging of patients with melanoma. DESIGN: A prospective cohort study of consecutive patients in which lymphatic mapping and sentinel lymph node (SLN) biopsy were performed on 114 melanoma patients with clinical stage I and stage II disease. The SLNs were bivalved, and half of each specimen was submitted for routine pathological examination. The other half was submitted for molecular detection of submicroscopic metastases using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase messenger RNA as a marker for the presence of melanoma cells. Patient follow-up averaged 28 months. SETTING: A major university-based melanoma referral center at a National Cancer Institute-designated cancer center. PATIENTS: A total of 114 patients with newly diagnosed cutaneous malignant melanoma who were at risk for regional nodal metastases. MAIN OUTCOME MEASURE: Melanoma recurrence and overall survival. RESULTS: Twenty-three patients (20%) had pathologically positive SLNs, and all of these patients were also RT-PCR positive. Of the 91 pathologically negative patients, 44 were RT-PCR negative and 47 were RT-PCR positive. There was a recurrence rate among 14 (61%) of the 23 patients who were both pathologically and RT-PCR positive and a recurrence rate among 1 (2%) of 44 patients who were both pathologically and RT-PCR negative. For patients who were upstaged by the molecular assay (pathologically negative, RT-PCR positive), there was a recurrence rate among 6 (13%) of 47 patients. The differences in recurrence rates and overall survival between the pathologically negative, RT-PCR-negative and pathologically negative, RT-PCR-positive patient groups were statistically significant (P= .02 for disease-free survival and for overall survival). In both univariate and multivariate regression analyses, the histological and RT-PCR status of the SLNs were the best predictors of disease-free survival. CONCLUSIONS: The use of an RT-PCR assay for detection of submicroscopic melanoma metastases in SLNs improved the prediction of melanoma recurrence and overall survival over routine pathological examination.
Asunto(s)
Metástasis Linfática/patología , Melanoma/patología , Monofenol Monooxigenasa/genética , Estadificación de Neoplasias/métodos , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Cutáneas/patología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/genética , Masculino , Melanoma/genética , Melanoma/mortalidad , Melanoma/secundario , Persona de Mediana Edad , Estudios Prospectivos , ARN Neoplásico/análisis , Cintigrafía , Análisis de Regresión , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/mortalidad , Análisis de SupervivenciaRESUMEN
Electrochemotherapy (ECT) enhances the effectiveness of chemotherapeutic agents by administering the drug in combination with short intense electric pulses. ECT is effective because electric pulses permeabilize tumour cell membranes and allow non-permeant drugs, such as bleomycin, to enter the cells. The aim of this study was to demonstrate the anti-tumour effectiveness of ECT with bleomycin on cutaneous and subcutaneous tumours. This article summarizes results obtained in independent clinical trials performed by five cancer centres. A total of 291 cutaneous or subcutaneous tumours of basal cell carcinoma (32), malignant melanoma (142), adenocarcinoma (30) and head and neck squamous cell carcinoma (87) were treated in 50 patients. Short and intense electric pulses were applied to tumours percutaneously after intravenous or intratumour administration of bleomycin. The tumours were measured and the response to the treatment evaluated 30 days after the treatment. Objective responses were obtained in 233 (85.3%) of the 273 evaluable tumours that were treated with ECT. Clinical complete responses were achieved in 154 (56.4%) tumours, and partial responses were observed in 79 (28.9%) tumours. The application of electric pulses to the patients was safe and well tolerated. An instantaneous contraction of the underlying muscles was noticed. Minimal adverse side-effects were observed. ECT was shown to be an effective local treatment. ECT was effective regardless of the histological type of the tumour. Therefore, ECT offers an approach to the treatment of cutaneous and subcutaneous tumours in patients with minimal adverse side-effects and with a high response rate.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Bleomicina/administración & dosificación , Terapia por Estimulación Eléctrica , Neoplasias Cutáneas/terapia , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/terapia , Adulto , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Bleomicina/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/terapia , Femenino , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/terapia , Humanos , Inyecciones Intralesiones , Inyecciones Intravenosas , Masculino , Melanoma/tratamiento farmacológico , Melanoma/terapia , Persona de Mediana Edad , Neoplasias de las Glándulas Salivales/tratamiento farmacológico , Neoplasias de las Glándulas Salivales/terapia , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
BACKGROUND: Electrochemotherapy (ECT) is performed by locally administering a chemotherapeutic agent in combination with electric pulses. Previous clinical studies have demonstrated the effectiveness of ECT. In these initial trials, the drug was administered intravenously, followed by administration of electric pulses directly to the tumor. This study was initiated to determine whether an intralesional injection of the drug in combination with electric pulses could provide an improved result. A group of 34 patients was studied. METHODS: The dose of intralesional bleomycin was based on tumor volume. This was followed 10 minutes later by 6 or 8 99-microsec pulses of electricity at an amplitude of 1.3 kV/cm. Both the bleomycin and the electric pulses were administered after 1% lidocaine with epinephrine solution was injected around the treatment site. RESULTS: All patients responded to the treatment. Responses were observed in 142 (99%) of 143 metastatic nodules or primary tumors within 12 weeks, with complete responses observed in 130 (91%) of the nodules. No complete responses were observed in nodules treated with bleomycin only or electric pulses only. Random biopsies confirmed the clinical findings. All patients tolerated the procedure well, and no significant side effects were noted. Muscle contraction was evident during administration of each electric pulse but promptly subsided after the pulse. CONCLUSIONS: ECT was shown to be an effective local treatment for cutaneous malignancies. The results suggest that ECT may have a tissue-sparing effect and result in minimal scarring. ECT may be a suitable alternative therapy for the treatment of basal cell carcinoma, local or regional recurrent melanoma, and other skin cancers.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Bleomicina/uso terapéutico , Terapia por Estimulación Eléctrica , Neoplasias Cutáneas/terapia , Adulto , Anciano , Carcinoma Basocelular/patología , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Femenino , Humanos , Masculino , Melanoma/patología , Melanoma/terapia , Persona de Mediana Edad , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: A number of single agents have been tested in patients with carcinoma of the head and neck receiving palliative treatment. In general, 15-30% of patients achieve a partial response lasting 3-4 months. Treatment has not been shown to alter survival rates. It is clear that new drugs with potentially greater activity need to be identified. For this purpose, the Eastern Cooperative Oncology Group conducted a Phase II evaluation of paclitaxel. METHODS: Patients with recurrent, metastatic, or locally advanced, incurable squamous cell carcinoma of the head and neck were eligible. The dose and schedule tested was the maximum tolerable dose of 250 mg/m2 determined from Phase I trials using a 24-hour infusion schedule and granulocyte-colony stimulating factor support. Courses were given at 3-week intervals until progression of disease was documented. Dose modifications were specified for hematologic toxicity and for neurotoxicity. RESULTS: Thirty-four patients were registered on study and 30 were eligible. Severe or life-threatening granulocytopenia was the most frequent toxicity observed, occurring in 91% of patients. Prior to response evaluation, one patient died of sepsis and one died of a myocardial infarct. Response was observed in 40% of eligible patients (4 complete and 8 partial responses). The median duration of response was 4.5 months (range, 2-20 months), with a median survival of 9.2 months and a 1-year survival rate of 33%. CONCLUSIONS: These results indicate that paclitaxel is an active agent for the treatment of squamous cell carcinoma of the head and neck. Studies evaluating alternative infusion schedules and combination regimens currently are underway.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Paclitaxel/uso terapéutico , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/efectos adversosRESUMEN
BACKGROUND: The technique of sentinel lymph node (SLN) biopsy for melanoma provides accurate staging information because the histology of the SLN reflects the histology of the entire basin, particularly when the SLN is negative. METHODS: We combined two mapping techniques, one using vital blue dye and the other using radiolymphoscintigraphy with a hand-held gamma Neoprobe, to identify the SLN in 600 consecutive patients with stage I-II melanoma. The SLNs were examined using conventional histopathology and immunohistochemistry for S-100. RESULTS: Eighty-three (13.9%) patients had micrometastatic disease in the SLNs. Thirty percent of patients with primary melanomas greater than 4.0 mm in thickness had positive SLNs, followed by 48 of 267 (18%) of patients with tumors between 1.5 mm and 4 mm, and 12 of 169 (7%) of those with lesions between 1.0 mm and 1.5 mm. No patient with a tumor less than 0.76 mm in thickness had a positive SLN. Sixty-four of the 83 SLN-positive patients consented to undergo complete lymph node dissection (CLND), and five of 64 (7.8%) of the CLNDs were positive. All patients with positive CLNDs had tumor thicknesses greater than 3.0 mm. CONCLUSIONS: The rate of SLN-positive patients increases with increasing thickness of the melanoma. SLN-positive patients with primary lesions less than 1.5 mm in thickness may have disease confined to the SLN, thus rendering higher-level nodes free of disease, and may not require a CLND.
Asunto(s)
Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Melanoma/cirugía , Neoplasias Cutáneas/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Niño , Extremidades/diagnóstico por imagen , Extremidades/patología , Extremidades/cirugía , Femenino , Estudios de Seguimiento , Cámaras gamma , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Inmunohistoquímica , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Masculino , Melanoma/diagnóstico por imagen , Melanoma/patología , Melanoma/secundario , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Cintigrafía , Radiofármacos , Colorantes de Rosanilina , Proteínas S100/análisis , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Azufre Coloidal Tecnecio Tc 99m , Neoplasias Torácicas/diagnóstico por imagen , Neoplasias Torácicas/patología , Neoplasias Torácicas/cirugíaRESUMEN
Contrary to the trend of early diagnosis observed in other parts of the world, in Florida melanoma is still being discovered in the more advanced stages. This is characterized by thicker lesions at diagnosis, which are hallmarked by bleeding, itching, ulceration, and increased vertical growth. In a study of 1,626 cutaneous melanoma patients at the H. Lee Moffitt Cancer Center in Florida, three prognostic factors, tumor thickness, Clark level, and presence of ulceration in the primary tumor, have remained relatively constant over an eight-year period (1987-1994). Despite the lack of change in tumor thickness in the last four years, mortality rate is decreasing, possibly due to more effective treatments. Regardless of these apparent improvements in mortality rates, definite progress must be made in the early detection of malignant melanoma through the initiation of statewide programs of lay public and professional education. In addition, it is proposed that the establishment of statewide screening programs of the Caucasian population with skin phenotypes 1 and 2 will also facilitate the early diagnosis of melanoma in the future, improve the outlook for these patients, and begin to address a major public health problem in the state of Florida.
Asunto(s)
Brotes de Enfermedades , Melanoma/epidemiología , Neoplasias Cutáneas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Educación Médica , Femenino , Florida/epidemiología , Educación en Salud , Humanos , Masculino , Tamizaje Masivo/métodos , Melanoma/mortalidad , Melanoma/patología , Melanoma/prevención & control , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Pronóstico , Salud Pública , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/prevención & control , Pigmentación de la Piel/genética , Úlcera Cutánea/patología , Población BlancaRESUMEN
OBJECTIVE: The purpose of this study is to emphasize the instrumental role of preoperative lymphoscintigraphy in the surgical treatment of patients with malignant melanoma. SUMMARY BACKGROUND DATA: The efficacy of lymphoscintigraphy is reflected in its ability to reveal cutaneous lymphatic drainage to regional nodal basins that are at risk for melanoma metastases but not necessarily discernable to be at risk through standard historical anatomical guidelines or clinical experience. This preoperative lymphatic mapping technique has contributed greatly to the accuracy and efficiency of staging procedures including sentinel node biopsy and elective lymph node dissection. PATIENTS AND METHODS: After informed consent, a selected series of four patients with primary melanomas located in watershed areas of the body (left neck, right mid-abdomen, right scapula, left back) and two patients with extremity melanomas (right distal forearm and left ankle) underwent pre-operative lymphoscintigraphy to identify all basins for metastases. RESULTS: In all of the cases, lymphatic drainage occurred in an unusual and unexpected basin that could not have been predicted clinically and in three of the cases the resected basins contained positive sentinel nodes. If not for the preoperative lymphoscintigraphy, these nodal basins would not have been resected and metastatic disease would have been left behind. In addition, the staging of the melanoma patient would have been inaccurate. CONCLUSION: If the sentinel node biopsy of elective lymph node dissection (ELND) were based on clinical predictions only, nodes equally at risk for metastatic disease would not have been resected and in some cases, nodal basins not at risk for metastases would have been resected unnecessarily. Without lymphoscintigraphy, the validity and efficacy of the ELND or the sentinel node biopsy for nodal staging is greatly compromised. These six case studies illustrate the difficulty of predicating lymphatic drainage from primary sites located on the head and neck, truck and even the extremities and demonstrate the indispensability of preoperative lymphoscintigraphy in the management of malignant melanoma.
Asunto(s)
Ganglios Linfáticos/diagnóstico por imagen , Linfa/metabolismo , Metástasis Linfática/diagnóstico por imagen , Melanoma/diagnóstico por imagen , Cuidados Preoperatorios , Neoplasias Cutáneas/diagnóstico por imagen , Piel/metabolismo , Abdomen , Adulto , Anciano , Tobillo , Dorso , Biopsia , Femenino , Antebrazo , Predicción , Humanos , Cuidados Intraoperatorios , Escisión del Ganglio Linfático , Metástasis Linfática/patología , Sistema Linfático/patología , Linfocintigrafia , Masculino , Melanoma/secundario , Melanoma/cirugía , Persona de Mediana Edad , Cuello , Escápula , Piel/patología , Neoplasias Cutáneas/cirugíaRESUMEN
BACKGROUND: Once individuals are diagnosed with malignant melanoma, they are at an increased risk of developing another melanoma when compared with the normal population. METHODS: To determine the impact of an intensive follow-up protocol on the stage of disease at diagnosis of subsequent primary melanomas, a retrospective query was performed of an electronic medical record database of 2,600 consecutively registered melanoma patients. RESULTS: Sixty-seven patients (2.6%) had another melanoma diagnosed at the time of presentation to the clinic or within 2 months (synchronous) and another 44 patients (1.7%) developed a second primary melanoma during the follow-up period (metachronous). For the 44 patients diagnosed with metachronous lesions, the Breslow mean tumor thickness for the first invasive melanoma was 2.27 mm compared with 0.90 mm for the second melanoma. The first melanomas diagnosed are thicker by an average of 3.8 mm (p = 0.008). The mean Clark level for the initial melanoma was greater than the mean level for subsequently diagnosed melanomas (p = 0.002). Twenty-three percent of the initial melanomas were ulcerated, whereas only one of the second primary lesions showed this adverse prognostic factor (p = 0.002). CONCLUSIONS: Once individuals are diagnosed with melanoma, they are in a high-risk population for having other primary site melanomas diagnosed and should be placed in an intensive follow-up protocol consisting of a complete skin examination.
Asunto(s)
Cuidados Posteriores , Melanoma/prevención & control , Neoplasias Primarias Múltiples/prevención & control , Neoplasias Primarias Secundarias/prevención & control , Adulto , Cuidados Posteriores/economía , Anciano , Anciano de 80 o más Años , Femenino , Florida/epidemiología , Humanos , Masculino , Melanoma/epidemiología , Melanoma/patología , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/patología , Pronóstico , Estudios RetrospectivosRESUMEN
We conducted a multiinstitutional phase II clinical trial to determine the toxicity, response, and survival rate of concurrent 72-h continuous infusion of etoposide and cisplatin in patients with metastatic breast cancer. A total of 26 women were enrolled, 4 of whom received no prior chemotherapy for metastatic disease. All patients were evaluated for toxicity, response, and survival employing the National Cancer Institute (NCI) Common Toxicity Criteria and the Eastern Cooperative Oncology Group (ECOG) response criteria. A total of 84 cycles of therapy were administered, median 3 (range 1 to 6). Severe grade 3 and grade 4 neutropenia occurred in 22 cycles (26%), and there were only 11 episodes (11%) of similar grade thrombocytopenia. Nausea and vomiting were seen in one third of cycles. A single patient (4%) had a complete remission, and seven patients (27%) had partial remissions for an overall objective response rate of 31% (95% confidence interval, 13 to 49%). Three of four patients (75%) without prior therapy for metastatic disease had objective responses. Median survival was 7 months. This combination regimen is active in extensively treated patients with metastatic breast cancer. It is responsible to further investigate the role of etoposide-cisplatin combination chemotherapy as firstline therapy for patients with metastatic breast cancer.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/secundario , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Adulto , Anciano , Antineoplásicos/efectos adversos , Antineoplásicos Fitogénicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Intervalos de Confianza , Etopósido/efectos adversos , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Náusea/inducido químicamente , Neutropenia/inducido químicamente , Inducción de Remisión , Tasa de Supervivencia , Trombocitopenia/inducido químicamente , Vómitos/inducido químicamenteRESUMEN
BACKGROUND: Electroporation is a process that causes a transient increase in the permeability of cell membranes. It can be used to increase the intracellular concentration of chemotherapeutic agents in tumor cells (electrochemotherapy; ECT). A clinical study was initiated to determine if this mode of treatment would be effective against certain primary and metastatic cutaneous malignancies. A group of six patients, three with malignant melanoma, two with basal cell carcinoma, and one with metastatic adenocarcinoma, were enrolled in the study. the treatment was administered in a two-step process. METHODS: Each patient received a 10 unit/m2 dose of bleomycin administered intravenously at 1 to 1.5 units/minute. This was followed by eight 99 microsecond pulses at an amplitude of 1.3 kV/cm administered directly to the tumors 5 to 15 minutes after the bleomycin was completely infused. Pulses were administered after the injection of 1% lidocaine solution around the treatment site. RESULTS: Two of three melanoma patients had objective responses. In these two patients, five of six treated tumors decreased in size, and three completely responded. Untreated tumors displayed continued growth. Objective responses were observed in both basal cell carcinoma (BCC) patients. One patient had partial responses in both treated tumors. The other patient had one of four primary BCCs respond completely, and the remaining three respond partially. Patients with metastatic breast adenocarcinoma showed complete responses in both treated nodules after ECT. All patients tolerated the treatment well with no residual effects from the electric pulses. CONCLUSIONS: ECT was an effective local treatment in the majority of nodules treated. The results thus far are very encouraging and the study is being continued.
Asunto(s)
Adenocarcinoma/terapia , Antibióticos Antineoplásicos/uso terapéutico , Bleomicina/uso terapéutico , Carcinoma Basocelular/terapia , Melanoma/terapia , Neoplasias Cutáneas/terapia , Estimulación Eléctrica Transcutánea del Nervio , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adulto , Anciano , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/farmacocinética , Bleomicina/efectos adversos , Bleomicina/farmacocinética , Carcinoma Basocelular/tratamiento farmacológico , Carcinoma Basocelular/metabolismo , Permeabilidad de la Membrana Celular/fisiología , Electrofisiología , Femenino , Humanos , Masculino , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Persona de Mediana Edad , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/metabolismo , Estimulación Eléctrica Transcutánea del Nervio/efectos adversosRESUMEN
BACKGROUND: The sentinel lymph node (SLN), the first node draining the primary tumor site, has been shown to reflect the histologic features of the remainder of the lymphatic basin in patients with melanoma. Intraoperative localization of the SLN, first proposed by Morton and colleagues, has been accomplished with the use of a vital blue dye mapping technique. Technical difficulties resulting in unsuccessful explorations have occurred in up to 20% of the dissections. OBJECTIVES: The authors aimed to define the SLN using gamma detection probe mapping and to determine whether intraoperative radiolymphoscintigraphy using technetium sulfur colloid and a hand-held gamma-detecting probe could be used to improve detection of all SLNs for patients with melanoma. METHODS: To ensure that all initial nodes draining the primary site were removed at the time of selective lymphadenectomy, the authors used intraoperative radiolymphoscintigraphy to confirm the location of the SLN, which was determined initially with the preoperative lymphoscintigram and the intraoperative vital blue dye injection. PATIENT POPULATION: The patient population consisted of 106 consecutive patients who presented with cutaneous melanomas larger than 0.75 mm in all primary site locations. RESULTS: The preoperative lymphoscintigram revealed that 22 patients had more than one lymphatic basin sampled. Two hundred SLNs and 142 neighboring non-SLNs were harvested from 129 basins in 106 patients. After the skin incision was made, the mean ratio of hot spot to background activity was 8.5:1. The mean ratio of ex vivo SLN-to-non-SLN activity for 72 patients who had SLNs harvested was 135.6:1. When correlated with the vital blue dye mapping, 139 of 200 (69.5%) SLNs demonstrated blue dye staining, whereas 167 of 200 (83.5%) SLNs were hot according to radioisotope localization. With the use of both intraoperative mapping techniques, identification of the SLN was possible for 124 of the 129 (96%) basins sampled. Micrometastases were identified in SLNs of 16 of the 106 (15%) patients by routine histologic analysis. CONCLUSION: The use of intraoperative radiolymphoscintigraphy can improve the identification of all SLNs during selective lymphadenectomy.