RESUMEN
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
Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.
Asunto(s)
Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Secuencia de Bases , Benzamidas , Cartilla de ADN , Progresión de la Enfermedad , Femenino , Humanos , Mesilato de Imatinib , Masculino , Melanoma/irrigación sanguínea , Melanoma/diagnóstico por imagen , Melanoma/secundario , Persona de Mediana Edad , Piperazinas/efectos adversos , Tomografía de Emisión de Positrones , Pirimidinas/efectos adversos , Neoplasias Cutáneas/irrigación sanguínea , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
In this phase II study we assessed the efficacy of bryostatin-1 (NSC 339555) in metastatic melanoma patients when given intravenously either once a week at a dose of 25 microg/m2 per day over 24 h for 3 weeks or at 40 microg/m2 per day over 72 h every 2 weeks. Treatment courses were repeated every 4 weeks. Patients who had received one prior chemotherapy regimen for advanced melanoma, with or without biotherapy, were randomized to one or the other bryostatin-1 dose schedules until 12 patients were registered to each arm. Because there was one confirmed response among the 12 patients who received the 72 h dose schedule, 25 more patients were added to that arm. No prophylactic medications were given. Objective tumour measurements were used to assess the efficacy of the regimen. The National Cancer Institutes common toxicity criteria were used to grade reactions. In total, 49 patients with metastatic melanoma, none having symptomatic brain metastasis, were studied. Of these, 12 patients received the 24 h bryostatin-1 regimen, while the remaining 37 received the 72 h regimen. One patient receiving the 72 h regimen had a partial response lasting over 7 months. Muscle pain occurred in over 90% of the patients and was the dose-limiting side effect of the 72 h regimen. Grade 3/4 nausea and vomiting were more common on the 24 h regimen than on the 72 h one (35% versus 5% of patients). There was no therapy-related thrombocytopenia. Neutropenia was mild and mainly limited to patients receiving the 72 h regimen. Bryostatin-1 has limited activity against melanoma when given by 72 h intravenous infusion.
Asunto(s)
Antineoplásicos/uso terapéutico , Lactonas/uso terapéutico , Melanoma/tratamiento farmacológico , Adolescente , Adulto , Anciano , Western Blotting , Brioestatinas , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Femenino , Humanos , Macrólidos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Isoformas de Proteínas , Proteína Quinasa C/biosíntesis , Proteína Quinasa C/metabolismo , Factores de TiempoRESUMEN
A phase II study was undertaken to determine the efficacy of Bexarotene in melanoma. Between November 1997 and April 1998, 19 patients were given Bexarotene in single daily oral doses of 450 mg/m2 in capsule form continuously. Nineteen patients, four with choroidal metastatic melanoma, were treated. No responses were seen. Five patients had stable disease, two of the four with choroidal melanoma, had tumor progression. Myelosuppression was mild. Grade 3 myalgia, asthenia, diarrhea, cold hands/feet, and mood changes were seen in one patient each. Changes in serum triglyceride and thyroxine levels were common. Bexarotene, as used in this study, is not effective against melanoma.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Coroides/tratamiento farmacológico , Neoplasias de la Conjuntiva/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Tetrahidronaftalenos/uso terapéutico , Adulto , Antineoplásicos/efectos adversos , Bexaroteno , Cápsulas , Neoplasias de la Coroides/patología , Neoplasias de la Conjuntiva/patología , Femenino , Humanos , Metástasis Linfática , Masculino , Melanoma/patología , Melanoma/secundario , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Cutáneas/patología , Tetrahidronaftalenos/efectos adversosRESUMEN
BACKGROUND: The authors tested a biotherapy regimen involving recombinant interferon-alpha-2a (rIFN-alpha-2a) and recombinant human interleukin-2 (rhIL-2), given in a "decrescendo" schedule over 5 days, for its activity and toxicity in 21 patients who previously had received chemotherapy for advanced melanoma. METHODS: Patients (15 men and 6 women) were given intravenous rhIL-2 at a dose of 18 MIU/m(2) over 6 hours, followed by 18 MIU/m(2) over 12 hours, then 18 MIU/m(2) over 24 hours, and finally 4.5 MIU/m(2)/day for 3 consecutive days. rIFN-alpha-2a (10 MIU/m(2)) was given subcutaneously on Days 1-5. Courses were repeated every 4 weeks. Tumor sites were measured every 8 weeks. Toxicity was recorded using National Cancer Institute Common Toxicity Criteria. RESULTS: No major objective responses were noted. The median number of courses given was two. The median time to progression was 2 months and the median survival was 6 months (range, 2-25 months). However, 2 patients with melanoma involving >/= 2 visceral organs (1 with a high baseline serum lactate dehydrogenase level) and a third with soft tissue metastases achieved durable control of disease and were alive a median of 30+ months later. A fourth patient had a palliative response with reversal of melanosis and a survival of 7 months. This regimen was well tolerated and resulted in no serious long term adverse effects. CONCLUSIONS: The response rate for this regimen was no greater than 10% with Type I and II errors each not exceeding 10%. Nevertheless, occasional durable control of disease and the nonoverlapping toxicity profile with prior chemotherapy support consideration of this regimen in these patients who have limited second-line treatment options.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interferón-alfa/administración & dosificación , Interleucina-2/administración & dosificación , Melanoma/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Recuento de Células Sanguíneas , Citocinas/uso terapéutico , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Interleucina-2/efectos adversos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Proteínas Recombinantes , Terapia RecuperativaRESUMEN
A phase II study was undertaken to determine the efficacy of tirapazamine combined with cisplatin in patients with metastatic melanoma between April 1996 and April 1997. Tirapazamine 390 mg/m2, administered i.v. over 2 h, followed in 1 h by cisplatin 75 mg/m2 over 1 h, were used every 21 days to treat chemotherapy-naive patients with metastatic melanoma. Objective tumor measurements were used to assess efficacy of the regimen. NCI common toxicity criteria were used to grade toxicities. Forty-eight patients with metastatic melanoma of cutaneous or mucosal origin, none with symptomatic brain metastasis, were treated. Nine patients had a partial response, with an overall response rate of 20% (95% confidence interval: 9-33%). The median duration of response was 6 months. Grade 3 nausea, vomiting, anorexia, muscle cramps and fatigue occurred in fewer than 10% of patients. Neutropenia and thrombocytopenia were rare. This outpatient single-day administered tirapazamine-cisplatin regimen has definite activity in chemotherapy-naive patients with metastatic melanoma. Further studies in combination with other agents active against this disease are warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Melanoma/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Factores de Tiempo , Tirapazamina , Resultado del Tratamiento , Triazinas/administración & dosificación , Triazinas/efectos adversosRESUMEN
Our objective was to determine the clinical activity, toxicity, and immunological effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT) cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included nonanergic patients fully recovered after resection of 5 or more grams of metastatic melanoma. Treatment consisted of intradermal injections of 10(7) UVR-AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin testing was performed for delayed-type hypersensitivity (DTH) determinations before the first, fourth, seventh, and subsequent treatments. Forty-two patients were treated, 18 in the adjuvant setting and 24 with measurable disease. Among the latter group, there were two durable responses in soft-tissue sites and in a bone metastasis. Treatment was well tolerated. Thirty-five patients were assessable for immunological parameters; 10 of these patients, including the 2 responders, demonstrated early induction of PBMC cytotoxicity against AT cells that persisted up to 10 months on treatment before falling to background levels. In five of seven patients, the fall-off heralded progressive disease. Late induction of a weak DTH reaction to AT cells was observed in eight patients. Active immunotherapy with UVR-AT + DETOX had modest but definite clinical activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH reactivity to AT cells supported a specific systemic immune effect of treatment, although the former more closely followed disease course in this study.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Vacunas contra el Cáncer , Proteínas del Citoesqueleto/uso terapéutico , Inmunoterapia , Lípido A/análogos & derivados , Melanoma/inmunología , Melanoma/terapia , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/terapia , Rayos Ultravioleta , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/sangre , Neoplasias Óseas/inmunología , Neoplasias Óseas/secundario , Neoplasias Óseas/terapia , Citotoxicidad Inmunológica , Combinación de Medicamentos , Femenino , Humanos , Hipersensibilidad Tardía , Inmunidad Activa , Inmunoglobulina G/sangre , Lípido A/uso terapéutico , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Neoplasias de los Tejidos Blandos/inmunología , Neoplasias de los Tejidos Blandos/terapia , Tasa de Supervivencia , Factores de TiempoRESUMEN
PURPOSE: The current American Joint Commission on Cancer (AJCC) staging system distinguishes between soft tissue and visceral metastases in advanced (stage IV) melanoma. We sought to verify these staging criteria and to identify prognostic variables that could be used to evaluate the impact of systemic therapy on long-term survival during the prior decade. PATIENTS AND METHODS: We conducted a retrospective study of patients with advanced cutaneous melanoma enrolled in clinical trials between 1979 and 1989 at The University of Texas M.D. Anderson Cancer Center. Pretreatment age, sex, number of organs with metastases, serum levels of lactate dehydrogenase (LDH) and albumin, and period of enrollment were analyzed using a Cox proportional hazards model of survival. RESULTS: In univariate and multivariate analyses that involved 318 stage IV patients, normal serum levels of LDH and albumin, soft tissue and/or single visceral organ metastases (especially lung), female sex, and enrollment late in the decade were independent positive predictors for survival. In multivariate analyses, the current AJCC criteria did not significantly predict outcome. Systemic treatment response did not bias these results, and only 4% of patients had a complete response. Patients who lived more than 2 years (11%) had a mix of favorable prognostic characteristics and a high frequency of systemic or surgically induced complete response. CONCLUSION: This study supports the use of stratification parameters that reflect the favorable prognostic impact of soft tissue or single visceral organ metastases and normal serum levels of LDH and albumin at time of enrollment in advanced melanoma trials. Improved survival over the prior decade probably reflects advances in diagnostic and palliative interventions.
Asunto(s)
Melanoma/secundario , Melanoma/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Análisis de SupervivenciaRESUMEN
Ninety-six patients with metastatic melanoma treated with two consecutive tirapazamine-cisplatin combination chemotherapy regimens were followed for signs of therapy-related ocular toxicity. Baseline and follow-up data were obtained such that each patient acted as his own control. A battery of vision-related tests was performed. These included: best corrected visual acuity, color vision, retinal fundus examination and electro-oculograms (EOG). A brief health-related quality of vision test was administered at each follow-up visit to detect and evaluate self-perceived changes in visual status. In the first study, 48 patients received i.v. tirapazamine over 2 h at 260 mg/m2 (group 1) while in the second study 48 patients (group 2) received i.v. tirapazamine at 390 mg/m2. Visual system assessment was conducted at three timepoints: first at baseline, then at 6 weeks post-baseline, i.e. after two courses of chemotherapy and visit two upon discontinuation of therapy. There was no difference in visual acuity between group 1 and group 2 at baseline, follow-up 1 or at follow-up 2. Grouped data indicate that visual acuity was not affected by either dosage of chemotherapy. Group 1 at baseline found 15% below the normal EOG cutoff point, increasing to 23% at follow-up 1 and increasing at follow-up visit 2 to 33%. Group 2 demonstrated the same EOG findings, but the results were more magnified: baseline, 24%; follow-up 1, 44%; and follow-up 2, 44%. After eliminating those with abnormal color vision baselines, 21% (nine of 42) group 1 patients demonstrated abnormal color vision total error scores at follow-up 1 and 16.7% (four of 24) at follow-up 2. Few individuals showed changes in the higher dosage group. With the exception of one person in each dosage group, all changes were along the blue-yellow (tritan) axis, which is associated with acquired color defects. Of 96 patients examined, proven fundus changes were found in only four subjects. These fundus findings included retinal hemorrhages, retinal nerve fiber layer infarcts (cotton wool spots) and small retinal pigment epithelium detachments. There was no systematic statistical significant difference among the various measures of visual system outcome between groups or test times. Data from all tests for individual patients in both groups reveals a sporadic distribution of changes in visual system tests. If toxicity were pronounced, one would expect consistency in the findings and all or most of the assessment tests would be abnormal for a particular patient. However, patients who were abnormal on one measure of acuity were not necessarily abnormal on the other measures.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Melanoma/tratamiento farmacológico , Visión Ocular/efectos de los fármacos , Adulto , Anciano , Análisis de Varianza , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Percepción de Color/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Tirapazamina , Triazinas/administración & dosificación , Triazinas/efectos adversos , Agudeza Visual/efectos de los fármacosRESUMEN
PURPOSE: A phase II study was undertaken to determine the efficacy of tirapazamine (TPZ) combined with cisplatin (cDDP) in patients with metastatic melanoma. PATIENTS AND METHODS: Between June 1994 and November 1995, 48 patients with metastatic melanoma were treated with TPZ (260 mg/m2, administered intravenously over two hours) followed in one-hour by cDDP (75 mg/m2 over one hour) every 21 days. Sixteen patients had received prior chemotherapy, and 13 of these had failed to respond to prior cDDP. None of the patients had symptomatic brain metastasis. RESULTS: Nine patients had partial responses, with an overall response rate of 19% (95% confidence interval (95% CI) of 9%-33%). The median duration of response was six months. None of the responders had received prior chemotherapy. Responses were seen in 8 (33%, confidence interval of 16%-55%) of 24 patients with primary cutaneous melanoma who had received no prior chemotherapy and in the only patient with previously untreated conjunctival melanoma. There were no responders among the seven patients with choroidal melanoma and 16 patients with previously treated cutaneous melanoma. Two patients with partial responses were rendered free of gross disease surgically three months after completing eight courses of TPZ-cDDP; they remain free of tumor recurrence. Responses were seen in lymph nodes (27%), lung (26%), skin (20%), adrenal gland (20%), soft tissues (17%) and liver (17%). Common toxicities included muscle cramps, fatigue, gastrointestinal effects and peripheral neuropathy. Fatigue, nausea, vomiting, anorexia, and muscle cramps were grade 3 or 4 in less than 10% of the courses. Neutropenia and thrombocytopenia were rare. CONCLUSION: The TPZ-cDDP combination has definite activity against chemotherapy-naïve patients with cutaneous melanoma and warrant further studies in combination with other cytotoxic agents.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Femenino , Humanos , Masculino , Melanoma/secundario , Persona de Mediana Edad , Tirapazamina , Triazinas/administración & dosificaciónRESUMEN
PURPOSE: A phase II study was undertaken to determine the efficacy of docetaxel in patients with metastatic malignant melanoma. PATIENTS AND METHODS: Between June 1992 and March 1994, 40 patients with metastatic malignant melanoma and no prior chemotherapy were treated with docetaxel 100 mg/m2 administered intravenously over 1 hour every 21 days. None of the patients had brain metastasis. Toxicity and follow-up data are provided. RESULTS: One patient had a histologically confirmed complete response that lasted for 14+ months. Four patients had partial responses, bringing the overall response rate to 12.5% (95% confidence interval [CI], 6% to 30%). A patient with a partial response had a single chest-wall metastasis and was rendered free of disease surgically after a maximal response to docetaxel and remained free of tumor recurrence after 18+ months. Tumor was stabilized in 22 patients. The overall median survival time was 13 months. The main hematologic toxicity was neutropenia, which was severe but transient. Peripheral neuropathy was the limiting nonhematologic toxicity in three patients. Other important toxicities included cutaneous toxicity, fluid retention, oral mucositis, and hypersensitivity reactions. Preadministration of dexamethasone and diphenhydramine reduced the incidence of hypersensitivity reactions, cutaneous toxicities, and fluid retention. CONCLUSION: Docetaxel has definite but low-level activity against malignant melanoma. Further investigation of this drug should be conducted in multidrug combination programs.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Melanoma/tratamiento farmacológico , Paclitaxel/análogos & derivados , Neoplasias Cutáneas/tratamiento farmacológico , Taxoides , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Fitogénicos/efectos adversos , Docetaxel , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Paclitaxel/efectos adversos , Paclitaxel/uso terapéuticoRESUMEN
BACKGROUND: Liver metastasis develops in approximately two-thirds of patients with recurrent uveal melanoma. Despite therapy, the median survival of those with liver metastasis is 5 to 7 months. The recognition of a grave prognosis associated with liver metastasis has led to evaluation of new modalities of therapy, including the use of regional therapies such as intrahepatic arterial chemotherapy and either embolization or chemoembolization of hepatic metastases. In this study, the results of an institutional experience over the past 2 decades are reviewed and prognostic factors that affect survival from the time the liver metastasis is diagnosed are assessed. METHODS: In this study of 201 patients with uveal melanoma involving the liver who were treated at M. D. Anderson Cancer Center between 1968 and 1991, the authors restrospectively reviewed the cases and compared the results of systemic therapies, hepatic intra-arterial chemotherapies, and chemoembolization of liver metastases. Cox's multivariate analysis and stepwise logistic regression were then computed to determine significant prognostic variables. RESULTS: The systemic therapies produced a response rate of less than 1%. Chemoembolization was the most effective treatment, inducing responses in 36% of patients. Survival curves were calculated using the life-table method of Kaplan and Meier. Patient- and tumor-related characteristics were examined and their relation to on survival from the time of diagnosis of liver metastasis was determined. Levels of serum alkaline phosphatase, total bilirubin, and lactic dehydrogenase plus response to treatment showed a strong relation to survival. In contrast, univariate analysis showed that patient age and gender, metastasis free interval, presence of extrahepatic metastasis, and type of therapy for liver metastasis did not influence survival. Multivariate stepwise regression analysis identified serum alkaline phosphatase and metastasis free interval as the main independent prognostic factors for survival after liver metastasis diagnosis. CONCLUSIONS: Of the three modalities of therapy used for choroidal melanoma metastatic to the liver, only chemoembolization using cisplatin-based regimens produced a meaningful response rate. Information from this analysis can be used to predict the outcome of patients with uveal melanoma metastatic to the liver. Patients with metastatic ocular melanoma confined to the liver should be treated with chemoembolization and should not be included in chemotherapy trials designed for cutaneous melanoma.
Asunto(s)
Neoplasias Hepáticas/secundario , Melanoma/secundario , Neoplasias de la Úvea/patología , Adulto , Anciano , Anciano de 80 o más Años , Fosfatasa Alcalina/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bilirrubina/sangre , Quimioembolización Terapéutica , Femenino , Humanos , L-Lactato Deshidrogenasa/sangre , Tablas de Vida , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/terapia , Modelos Logísticos , Masculino , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Úvea/mortalidadRESUMEN
Thirty-two patients with untreated advanced colorectal carcinoma received high-dose methotrexate pretreatment followed sequentially by 5-fluorouracil (5-FU). Patients were randomized to receive high-dose methotrexate pretreatment at one of two intervals (0 h or 3 h before 5-FU). There were 16 patients in each study arm. The median methotrexate dose was 1,000 mg/m2 (range, 600-1,200 mg/m2) and that of 5-FU was 1,000 mg/m2 (range, 800-1,200 mg/m2). Treatments were repeated every 21 days. Three patients achieved partial remission (1 in the 3-h interval arm and 2 in the 0-h interval arm). As the response rate using this regimen was noted to be 9% with a less than 5% chance of achieving a response rate higher than 20%, we terminated this study although the therapy resulted in mild-to-moderate but infrequent toxicity. We thus conclude that pretreatment with high-dose methotrexate given at short intervals followed by 5-FU has no significant activity against colorectal carcinoma.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adenocarcinoma/sangre , Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Sangre/efectos de los fármacos , Ensayos Clínicos como Asunto , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/mortalidad , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Distribución Aleatoria , Inducción de Remisión , Factores de TiempoRESUMEN
The data on 62 patients with germinal testicular tumors seen at King Faisal Specialist Hospital and Research Centre between January 1977 and June 1983 were analyzed to determine the epidemiologic and clinical characteristics of the disease in Saudi Arabia. Fifty-seven patients were Saudis. The geographic distribution of Saudi patients seemed to coincide with population concentrations. Testicular seminomas (TS) and non-seminomatous testicular tumors (NSTT) comprised 50% each. The mean age was 41 and 27.8 years for TS and NSTT, respectively. Fifteen patients had cryptorchidism of the involved testicle. Three patients with NSTT had a history of trauma to the involved testicle. The most common presentations were painless testicular swelling (51.6%), painful swelling (16%), and abdominal or inguinal swelling (21%). The delay between the onset of symptoms and referral (mean 15 months) was considerable. Eighty percent of patients with NSTT and 45% of those with TS had advanced disease at referral.
Asunto(s)
Disgerminoma/epidemiología , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias Testiculares/epidemiología , Adulto , Humanos , Masculino , Arabia SauditaRESUMEN
Acivicin, an amino acid antibiotic, was administered to 36 adult patients with previously treated metastatic colorectal cancer. The starting dose for good-risk patients was 15 mg/m2/day day given as a short intravenous infusion on 5 consecutive days every 3 weeks. Patients previously treated with radiation therapy, mitomycin, or nitrosoureas and those with inadequate bone marrow reserve received 12 mg/m2 on the same schedule. In 33 evaluable patients, one partial response occurred. Sixteen patients had stable disease with a median time to disease progression of 15 weeks (range 9-27) and a median survival of 8 months. The median survival of the whole group was, however, less than 6 months. Myelotoxicity was mild and resulted in no significant complications. Nonhematological toxicity primarily consisted of nausea, vomiting, drowsiness, depression, and altered mentation. Acivicin given by this schedule is inactive at these dose levels in previously treated patients with colorectal carcinoma.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Isoxazoles/uso terapéutico , Oxazoles/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Adulto , Anciano , Antibióticos Antineoplásicos/efectos adversos , Evaluación de Medicamentos , Femenino , Humanos , Isoxazoles/efectos adversos , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Metástasis de la Neoplasia , Vómitos/inducido químicamenteRESUMEN
Thirty-three patients with metastatic colorectal carcinoma were treated with sequential conventional dose methotrexate (60 mg/m2) followed within 1 hour by 5-fluorouracil (1000 mg/m2) every 3 weeks. Thirty of 33 patients were assessable for response. One patient (3%) achieved a partial remission (3.5 months). Three patients demonstrated minor tumor regressions. In an additional 17 patients, tumor stabilization was observed. The treatments were tolerated without any significant morbidity. A disappointingly low response rate was observed in our study as opposed to previous reports. Further clinical studies are necessary to establish the optimum dose levels and scheduling of sequential methotrexate and 5-fluorouracil.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Evaluación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Factores de TiempoRESUMEN
One hundred five patients with advanced non-small cell lung cancer were randomized to receive thymosin fraction V immunotherapy during remission induction chemotherapy with vindesine, doxorubicin, and cisplatin (VAP). Fifty-four patients received VAP alone. Fifty-one patients received VAP + thymosin. Both groups were comparable; most patients were male, with a good performance status and with the diagnosis of adenocarcinoma. Among 99 evaluable patients, response was seen in 24 (2 CRs, 22 PRs) of 53 (45%) patients treated with VAP and 10 (all PRs) of 46 (22%) patients treated with VAP + thymosin (p = 0.03). VAP-treated patients responded better than those treated with VAP + thymosin in each tumor category: adenocarcinoma, 50% of 36 patients versus 22% of 27 patients; squamous cell carcinoma, 29% of 14 patients versus 21% of 13 patients; undifferentiated carcinoma, 67% of three patients versus 17% of six patients. Median survival duration was 34 weeks versus 25 weeks in favor of the VAP-treated group (p = 0.14). Thymosin treatment resulted in decreased graft-vs.-host reaction (p = 0.01) and increased suppressor effect on normal mitogen response to Con-A (p = 0.17). The activity of VAP chemotherapy is comparable with the most effective multidrug regimens of the present time in patients with advanced non-small cell tumors. The addition of thymosin immunotherapy appeared to have a negative effect on the activity of VAP.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/terapia , Timosina/análogos & derivados , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/inmunología , Adenocarcinoma/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma/tratamiento farmacológico , Carcinoma/inmunología , Carcinoma/terapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/terapia , Ensayos Clínicos como Asunto , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Estudios de Evaluación como Asunto , Femenino , Humanos , Inmunidad Celular/efectos de los fármacos , Inmunoterapia , Leucopenia/etiología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Masculino , Persona de Mediana Edad , Prednisolona/administración & dosificación , Prednisolona/efectos adversos , Estudios Prospectivos , Trombocitopenia/etiología , Timosina/uso terapéutico , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
This study of 783 patients with histologically confirmed gastric carcinoma has confirmed the importance of several previously recognized patient- and tumor-related characteristics related to prognosis and identified some new ones. Of the tumor-related factors, the ones that showed the strongest relationship to survival following curative gastric resection were tumor stage, histologic type, breach of lymph-node capsule, sinus histiocytosis, and gross appearance. Of the tumor- and patient-related factors, the ones that showed the strongest relationship to survival from time of diagnosis of surgically noncurable disease were status of primary, liver metastasis, serum bilirubin level, ascites, extent of tumor burden, and weight loss. The effect of treatment with 5-fluorouracil (5-FU) on survival duration was at best only minimal. Only those patients who received two or more cycles of 5-FU therapy had survival advantage over the remaining patients. The use of regression analysis has made it possible to make predictions of the prognosis of the patients. These predictions could be used in future studies to determine comparability of prognosis of various groups included in different studies and different arms of a randomized study.
Asunto(s)
Adenocarcinoma/mortalidad , Linfoma/mortalidad , Sarcoma/mortalidad , Neoplasias Gástricas/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adulto , Anciano , Femenino , Fluorouracilo/uso terapéutico , Gastrectomía , Humanos , Neoplasias Hepáticas/secundario , Metástasis Linfática , Linfoma/patología , Linfoma/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Análisis de Regresión , Sarcoma/patología , Sarcoma/terapia , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapiaRESUMEN
In this study of 232 patients with histologically confirmed large bowel carcinoma, patient- and tumor-related characteristics were examined and their effect on prognosis was determined. Serum alkaline phosphatase and albumin concentrations, symptom duration prior to diagnosis of the primary tumor, and the status of the primary tumor showed the strongest relationship to survival after diagnosis of surgically noncurable disease. Patients who had normal serum alkaline phosphatase and albumin concentrations, patients whose symptoms lasted over 12 months before diagnosis, and patients whose primary tumor had been resected before diagnosis of noncurable disease had a good prognosis. Performance status, weight loss, sex, presence of liver metastasis, hemoglobin concentration, and absolute lymphocyte or monocyte counts in the peripheral blood, at time of diagnosis of surgically noncurable disease, were significant factors when examined individually. One hundred seventy-nine patients with metastatic colorectal cancer confined to the liver were selected from 601 patients who received chemotherapy for advanced colorectal cancer over 10-year periods to compare the efficacy of hepatic-artery infusion therapy with that of intravenous 5-fluoropyrimidine--containing chemotherapy. The two groups were similar with respect to prognostic factors. The hepatic-artery infusion chemotherapy produced a higher response rate than intravenous chemotherapy, but did not result in significant prolongation of survival.
Asunto(s)
Neoplasias del Colon/mortalidad , Neoplasias Hepáticas/secundario , Pirimidinas/administración & dosificación , Neoplasias del Recto/mortalidad , Fosfatasa Alcalina/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recuento de Células Sanguíneas , Neoplasias del Colon/tratamiento farmacológico , Femenino , Arteria Hepática , Humanos , Infusiones Intraarteriales , Infusiones Parenterales , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Masculino , Pronóstico , Neoplasias del Recto/tratamiento farmacológico , Albúmina Sérica/análisisRESUMEN
Forty-one patients with recurrent primary malignant brain tumors were treated with 2,5-diaziridinyl 3,6-bis (carboethoxyamino), 1,4-benzoquinone (AZQ) at an initial dose of 6-8 mg/m2/day X 5 days. Courses were repeated monthly upon recovery of myelosuppression. Six of 25 evaluable patients (24%) showed definite tumor regression, and 7 (28%) showed disease stability as determined by monthly CT scans and neurologic examination. For all patients receiving one course of AZQ, the response rate was 16% (6 of 37 patients) and the stable disease rate 19%. The estimated median time to tumor progression with AZQ was 54 weeks for the responding patients and 36 weeks for the stable patients. Toxicity consisted of myelosuppression, primarily thrombocytopenia, which was delayed and cumulative. Other toxicities were uncommon. Further clinical trials in patients with malignant primary brain tumors, including combination studies with other drugs, are indicated.