RESUMO
In patients with multiple myeloma, there is preclinical justification to combine arsenic trioxide (ATO and As(2)O(3)) with DVd (Doxiltrade mark, vincristine, and dexamethasone) for newly diagnosed patients. Eleven patients on this phase II trial received 0.15 mg/kg of ATO for five consecutive days followed by four cycles of DVd plus ATO with the ATO at 0.25mg/kg IV twice per week. The most common grade 3 toxicities were hyperglycemia, hyponatremia, and hypocalcemia. There were four partial and no complete responses. We could not demonstrate that the addition of ATO with this schedule improved the response rate of MM to DVd.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arsenicais/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Óxidos/administração & dosagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trióxido de Arsênio , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Avaliação de Medicamentos , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
BACKGROUND: The aim of the study was to evaluate the efficacy and tolerability of the combination of oxaliplatin, fluorouracil and leucovorin in patients with advanced esophagus cancer. PATIENTS AND METHODS: Thirty-five patients with recurrent or metastatic esophageal adenocarcinoma or squamous cell carcinoma were enrolled. Up to one prior chemotherapy regimen was allowed. All patients had bi-dimensionally measurable disease. Patients received oxaliplatin 85 mg/m2 as a 2-h infusion on day 1. Leucovorin (500 mg/m2) followed by fluorouracil bolus (400 mg/m2) and 22-h continuous infusion fluorouracil (600 mg/m2) was administered on days 1 and 2. Granulocyte colony stimulating factor was not routinely administered unless the patient developed febrile neutropenia or prolonged neutropenia. Treatment was repeated every 14 days. RESULTS: Of the thirty-five patients enrolled, all were evaluated for toxicity and 34 were evaluated for response. The overall response rate was 40% (95% confidence interval, 24% to 57%) with complete and partial response rates of 3% and 37%, respectively. The median response duration was 4.6 months, and the median overall survival was 7.1 months. One-year survival was 31%. The major toxicity noted was cumulative neutropenia, with 29% developing grade 4 toxicity. There was one treatment-related death secondary to neutropenic sepsis. The most common non-hematologic toxicity encountered with this regimen was cumulative peripheral neuropathy, with 26% experiencing grade 2 or 3 toxicity. CONCLUSIONS: The combination of oxaliplatin, leucovorin, and fluorouracil shows significant anti-tumor activity and a favorable toxicity profile in patients with metastatic carcinoma of the esophagus.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/secundário , Esquema de Medicação , Neoplasias Esofágicas/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Gástricas/patologia , Taxa de SobrevidaAssuntos
Acridinas/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Pirazóis/uso terapêutico , Acridinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Agranulocitose/induzido quimicamente , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/patologia , Avaliação de Medicamentos , Humanos , Neoplasias Renais/secundário , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Pirazóis/efeitos adversos , Trombocitopenia/induzido quimicamente , Vômito/induzido quimicamenteRESUMO
Hairy cell leukemia (HCL) is a chronic lymphoproliferative disease of B-cell origin manifested by pancytopenia and splenomegaly. Before 1980 the only effective treatment for HCL was splenectomy, which resolved the cytopenia but did not eliminate the disease from the bone marrow. In addition, the majority of patients progressed after splenectomy and required further treatment. Pentostatin (Nipent; SuperGen, San Ramon, CA) is a purine antimetabolite that was found in phase I studies to induce profound lymphocytopenia Although in vitro studies suggested that T lymphocytes were most sensitive to pentostatin, patients with B-cell chronic lymphatic leukemia and low-grade non-Hodgkin's lymphoma responded to treatment in the initial phase I trials. Due to evidence that the drug was effective in lymphoproliferative disease, patients with HCL were treated with pentostatin. The promising initial results led to phase II studies in both untreated and previously treated patients. These studies demonstrated that pentostatin was highly effective as a single agent, with complete responses seen in 60% to 90% of patients. These responses were durable without maintenance chemotherapy and were seen in patients previously treated with interferon or chemotherapy. Toxicity was usually mild, with nausea and skin rashes predominating. When seen, infections resulting from neutropenia occurred early in treatment. The high response rates and low toxicity suggest that pentostatin should be considered as one of the standard treatments for HCL.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Imunossupressores/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Pentostatina/uso terapêutico , Inibidores de Adenosina Desaminase , Antibióticos Antineoplásicos/efeitos adversos , Progressão da Doença , Toxidermias/etiologia , Inibidores Enzimáticos/uso terapêutico , Exantema/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Leucemia de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Pancitopenia/tratamento farmacológico , Pentostatina/efeitos adversos , Indução de Remissão , Esplenomegalia/tratamento farmacológico , Esplenomegalia/cirurgiaRESUMO
Older patients with acute myelogenous leukemia (AML) have overexpression of P-glycoprotein (Pgp+), and this has been shown to correlate quantitatively with therapeutic outcome. Since Pgp-mediated efflux of cytotoxic drugs can be inhibited by the cyclosporine analogue, PSC 833, we investigated the use of this agent with a 5-day mitoxantrone/etoposide regimen in patients over age 55 with newly diagnosed AML. Previous studies suggested a 33% incidence of grade IV/V non-hematologic toxicity with the use of mitoxantrone 10 mg/M(2) and etoposide 100 mg/M(2), each for 5 days, in this patient population. Since PSC 833 alters the pharmacokinetic excretion of MDR-related cytotoxins, this phase I dose-finding study was performed to identify doses of mitoxantrone/etoposide associated with a similar 33% incidence of grade IV/V non-hematologic toxicity, when given with PSC 833. Mitoxantrone/etoposide (M/E) doses were escalated in fixed ratio from a starting dose of M: 4 mg/M(2) and E: 40 mg/M(2), to M: 7 mg/M(2) and E: 70 mg/M(2), in successive cohorts of eight patients each. PSC 833 was well tolerated and the MTD of this M/E regimen with PSC 833 in this population was M: 6 mg/M(2) and E: 60 mg/M(2). The complete response (CR) rate for all patients was 50% (15/30) and was considerably higher for de novo than for secondary AML. These data suggest that the addition of PSC 833 to an M/E regimen for older patients with untreated AML is well tolerated but requires a reduction in M/E dosing to avoid increased toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Ciclosporinas/administração & dosagem , Ciclosporinas/farmacocinética , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/farmacocinética , Feminino , Humanos , Leucemia Mieloide/metabolismo , Leucemia Mieloide/mortalidade , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/farmacocinética , Análise de Sobrevida , Resultado do TratamentoRESUMO
We evaluated 9-aminocamptothecin (9-AC) in patients with metastatic or locally recurrent breast cancer who were no longer responsive to standard therapy. Patients were treated with 9-AC with a 72-hr continuous infusion given at a dose of 45 micrograms/m2/hr every 2 weeks. Granulocyte colony-stimulating factor 5 micrograms/kg was given subcutaneously for 7-10 days after completion of the treatment. Eighteen patients were treated, with all patients assessable for toxicity and 15 patients assessable for response. There were two partial responses seen in the 15 patients lasting 3.5 and 5 months, respectively. The major toxicity seen was myelosuppression, with 12 patients having grade 3 or greater granulocytopenia with four episodes of significant infectious complications. In addition, significant thrombocytopenia was seen in 14 patients. The other complications commonly seen were nausea and vomiting and alopecia. 9-AC given as a 3-day continuous infusion has limited activity in previously treated metastatic and locally recurrent breast cancer.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Camptotecina/análogos & derivados , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The aim of this study is to determine whether the addition of mitoxantrone to high dose cytarabine improves the outcome of treatment in patients with relapsed or refractory acute myeloid leukemia (AML). One hundred and sixty-two eligible patients, 14-76 years of age, with AML either in first relapse or that failed to respond to initial remission induction therapy, with no CNS involvement were randomized to receive therapy with cytarabine 3 gm/M2 i.v. over 2 h every 12 h for 12 doses on days 1-6 (Arm I) (HIDAC); or HIDAC plus mitoxantrone 10 mg/M2 i.v. daily on days 7 9 (Arm II) (HIDAC + M). Patients achieving complete remission were treated with three courses of consolidation including HIDAC (Ara-C 3 gm/M2 i.v. 12 h days 1 3; 2 gm/M2 over age 50) alone (ARM I) or with mitoxantrone (10 mg/M2 i.v. day 1) (ARM II). Among 162 patients (81 HIDAC, 81 HIDAC + M) evaluated for induction toxicity, there were 10 (12%) induction deaths with HIDAC and 13 (17%) with HIDAC + M (2-tailed P = 0.65). Most early deaths were due to infection and/or hemorrhage. Among 162 patients evaluated for responses to induction therapy, 26/81 (32%) HIDAC and 36/81 (44%) HIDAC + M patients achieved complete remission (two-tailed P = 0.15). Although this difference was not statistically significant in univariate analysis, it was after adjusting for the effects of WBC and PMN percentage in multivariate analysis (P=0.013). Median survivals from study entry were 8 months (HIDAC) and 6 months (HIDAC + M); 2-tailed logrank P = 0.58. Among 48 patients registered for consolidation, the median disease-free survivals from that registration were 8 months with HIDAC and 11 months with HIDAC + M (P = 0.60). There were three treatment-related deaths during consolidation (1 HIDAC, 2 HIDAC + M), all due to infections. In this randomized trial, the addition of mitoxantrone to high-dose cytarabine was associated with a trend toward a higher CR rate. There was less evidence for an advantage in disease-free or overall survival, although any such conclusion is limited by the size of the study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Idoso , Citarabina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Prognóstico , Recidiva , Resultado do TratamentoRESUMO
The standard treatment of multiple myeloma is systemic chemotherapy. Despite 30 years of drug development in myeloma, there are no new drug regimens significantly superior to melphalan and prednisone. In addition, phase II studies of new drugs in myeloma have been disappointing, with low response rates and no prolongation in survival. The topoisomerase I (topo I) inhibitors are a new class of anticancer agents with a wide spectrum of activity in human malignancies. Recent evaluation of the topo I inhibitor topotecan demonstrated activity in advanced myeloma, suggesting a possible role for these drugs in the treatment of this disease. Further evaluation of the mechanisms of resistance to topo I inhibitors, study of combination therapy with topotecan, and evaluation of other topo I poisons in multiple myeloma is proposed.
Assuntos
Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Inibidores da Topoisomerase I , Ensaios Clínicos Fase II como Assunto , HumanosRESUMO
PURPOSE: Topotecan is a topoisomerase I inhibitor with antitumor activity against hematologic and solid tumor malignancies. We evaluated its activity in refractory and relapsing multiple myeloma patients who had received one prior chemotherapeutic regimen. PATIENTS AND METHODS: Toptecan 1.25 mg/m2/d was administered as a 30-minute infusion for 5 days repeated every 3 weeks. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/d subcutaneously was administered after the first course of treatment if neutropenia was dose-limiting. RESULTS: Forty-six patients entered the study, with 43 patients eligible. The major toxicity was granulocytopenia with grade 3 or better occurring in 40 of 43 patients treated; 21 of 43 patients developed grade 3 or greater thrombocytopenia. Other significant toxicity included mild nausea in 23 patients and mild vomiting in 13 patients. The overall response rate (partial response or better) was 16% (95% confidence interval, 7% to 31%), with responses occurring in both relapsed and refractory patients. Responses have lasted 70 to 477+ days, with a median progression-free survival duration of 13 months and median survival time of 28 months. CONCLUSION: Topotecan has activity in refractory and relapsing multiple myeloma. Future investigation of topotecan in multiple myeloma including combination therapy and the study of other topoismerase I inhibitors is warranted.
Assuntos
Antineoplásicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Topotecan/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Recidiva , Taxa de Sobrevida , Topotecan/efeitos adversosRESUMO
Topotecan (S-9-dimethyl-10-hydroxycamptothecin hydrochloride SKF 104864-A) is a semisynthetic analog of the alkaloid camptothecin and, similar to the parent compound, a potent inhibitor of topoisomerase I. The cytotoxicity induced by topotecan appears due to interference with the normal breakage reunion reaction of topoisomerase I leading to DNA damage and cell death. Since preclinical studies of topotecan suggested antitumor activity against refractory solid tumors, a phase II trial of the drug was initiated in melanoma patients with recurrent and/or metastatic disease. Topotecan 1.5 mg/m2 was given as a daily 30-min infusion for 5 days and repeated every 21-28 days. Seventeen patients were entered into the treatment program with all evaluable for toxicity but I patient, inevaluable for response. There were no objective responses. Toxicity was predominantly severe myelosuppression, which occurred in 12 of 17 (70%) patients. Topotecan in this dose and schedule is inactive in malignant melanoma.
Assuntos
Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Inibidores Enzimáticos/uso terapêutico , Melanoma/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , TopotecanRESUMO
Merbarone, NSC 336628, is an investigational anticancer drug with activity against experimental animal tumors including melanoma. This paper presents results of a Phase II clinical study of merbarone in patients with biopsy proven stage IV malignant melanoma without prior chemotherapy and with no evidence of CNS involvement. Thirty-five patients with median age 58 (range 27-81), with performance status 0-2 were treated with merbarone 1000 mg/m2/day for five days by intravenous continuous infusion repeated every 3 weeks. All patients (21 males and 14 females) were evaluable for toxicity. Two patients were not evaluable for response having been removed from protocol treatment due to toxicity and received other treatment during the first course of chemotherapy. Among the evaluable patients there was one complete response in a supraclavicular lymph node lasting four months and one partial liver response lasting three months. The remaining thirty-one patients were non-responders. Of these one had a stable disease lasting 21 months. The overall objective response rate was 6% (2/35) with a 95% confidence interval of 1%-19%. Twenty-six of the 35 patients have died. The estimated median survival of the entire group was 9 months with a 95% confidence interval six to eleven months. Renal toxicity was dose-limiting and manifested as increasing serum creatinine (54% of patients), proteinuria (51%) and hematuria (9%). One patient experienced grade 4 creatinine increase, proteinuria and acute renal failure. Other toxicities included nausea (71%), vomiting (51%0, malaise (23%), weakness (20%), alopecia (17%), diarrhea (17), anorexia (14%) transaminase (SGOT, SGPT) increase (14%), constipation (14%), alkaline phosphatase or 5'nucleotidase increase (9%), and fever (9%). Hematologic toxicity (granulocytopenia, leukopenia, and anemia) was generally mild and infrequent (29%, only one patient had grade 4 granulocytopenia). Overall 9 patients (26%) had at least one grade 3 toxicity. We conclude that merbarone at this dose and schedule has detectable but minimal activity in the treatment of metastatic malignant melanoma and given the significant renal toxicity this schedule does not merit further evaluation in this disease.
Assuntos
Antineoplásicos/uso terapêutico , Drogas em Investigação/uso terapêutico , Melanoma/tratamento farmacológico , Tiobarbitúricos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Avaliação de Medicamentos , Drogas em Investigação/administração & dosagem , Drogas em Investigação/efeitos adversos , Feminino , Humanos , Infusões Intravenosas , Rim/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Melanoma/patologia , Melanoma/secundário , Pessoa de Meia-Idade , Tiobarbitúricos/administração & dosagem , Tiobarbitúricos/efeitos adversosRESUMO
Twenty-four patients with advanced hairy cell leukemia treated with 2'-deoxycoformycin (dCF) were studied after achieving complete remission to determine the impact of treatment on survival, disease-free survival, long-term complications of treatment, and response to retreatment. At a median follow-up time of 82 months (range, 54 to 104 months), 23 of 24 patients remain alive. One patient has died of recurrent disease refractory to treatment. Of the remaining 23 patients, 11 have relapsed at a median time of 30 months (range, 7 to 80 months) after treatment completion. Of these 11 patients, 7 have been retreated with dCF or 2'-chlorodeoxyadenosine (2-CdA), including one patient that was retreated twice. All seven patients have responded, with five patients achieving second complete remission. Two patients have had normalization of blood cell counts, but repeat bone marrows have not been performed. No serious infections have been seen in dCF-treated patients during follow-up. One case of Hodgkin's disease and three cases of skin malignancies have developed in these 24 patients. From initiation of treatment, survival is 93 months (range, 63 to 116 months). We concluded that dCF significantly prolongs the survival of patients with advanced hairy cell leukemia without resultant long-term complications. It is too early to predict if this therapy will be curative for the patients still in remission.
Assuntos
Leucemia de Células Pilosas/tratamento farmacológico , Pentostatina/uso terapêutico , Idoso , Medula Óssea/patologia , Carcinoma Basocelular , Carcinoma de Células Escamosas , Seguimentos , Doença de Hodgkin , Humanos , Leucemia de Células Pilosas/mortalidade , Neoplasias Primárias Múltiplas , Segunda Neoplasia Primária , Indução de Remissão , Terapia de Salvação , Neoplasias Cutâneas , Análise de Sobrevida , Resultado do TratamentoRESUMO
The Southwest Oncology Group (SWOG) studied the response rate and toxicity of merbarone (1,000 mg/m2 IV continuous infusion days 1-5, q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 36 eligible patients, there was one partial response for a response rate of 3% (95% C.I. 0.1-15%). There were no mixed responses. There were no treatment related deaths or adverse drug reactions. Significant anemia, diarrhea, and hypercalcemia were observed. Mild to moderate degrees of malaise/fatigue/lethargy, dizziness/vertigo, hyperglycemia, creatinine increase, nausea, vomiting, weight loss, pedal edema, dyspnea, and granulocytopenia were noted. Merbarone does not have significant activity as a single agent in advanced renal cell carcinoma.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Tiobarbitúricos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/secundário , Esquema de Medicação , Humanos , Infusões Intravenosas , Tiobarbitúricos/administração & dosagem , Tiobarbitúricos/efeitos adversosRESUMO
The sodium salt of pyrazine-2-diazohydroxide (PZDH; NSC 361456) was identified as an active congener of the antitumor lead pyridine-2-diazotate with enhanced chemical stability under physiological conditions. In a phase I trial of PZDH administered as a single i.v. bolus injection, 19 patients with refractory solid tumors received 44 courses of therapy at dose levels ranging from 50 to 350 mg/m2. No objective responses to PZDH were noted. Myelosuppression characterized by prolonged, delayed onset leukopenia and thrombocytopenia was the dose limiting toxicity. A maximum tolerated dose of 350 mg/m2 was identified for this treatment schedule. Nonhematological toxicity was limited to severe nausea and vomiting, experienced by all patients treated at the lower doses, although reasonably well controlled when antiemetics were given prior to chemotherapy. The plasma pharmacokinetics of PZDH was evaluated following a single course of therapy in 16 patients. Drug levels were monitored using a specific capillary gas chromatographic assay with a 1-ng/ml lower limit of quantitation. In patients treated with doses greater than 50 mg/m2, the concentration of PZDH in plasma declined in a distinctly triexponential manner and remained above 1.5 ng/ml for at least 8 h. However, the initial decay phase, characterized by a harmonic mean half-life of 3.9 +/- 3.5 (SD) min (range, 2.2-6.3 min), was the primary determinant of drug disposition, as indicated by its 85.5-93.1% contribution to the area under the plasma concentration-time profiles from time zero to infinity. The harmonic mean terminal half-life increased with escalations in dose from 2.7 +/- 0.8 h (n = 2) at 100 mg/m2 to 8.5 +/- 3.0 h at 350 mg/m2 (n = 6). Total plasma drug clearance was very similar in patients treated with doses of 50-250 mg/m2, exhibiting a mean value of 42.5 +/- 7.8 liters/h/m2 (n = 10); however, it was significantly lower at the 350 mg/m2 dose level, 27.2 +/- 6.6 liters/h/m2 (n = 6; P < 0.002), denoting a departure from linear pharmacokinetic behavior. The rather low steady state apparent volume of distribution, which ranged from 6.0 +/- 1.5 (50 mg/m2, n = 2) to 12.7 +/- 8.0 (350 mg/m2, n = 6) liters/m2, was indicative of limited distribution of the drug into body tissue. The absence of objective antitumor effects should not discourage continued evaluation of PZDH against solid tumors selected for probable sensitivity as indicated by preclinical testing. A dose of 250 mg/m2 on a single i.v. bolus schedule is recommended for these phase II trials.
Assuntos
Antineoplásicos/farmacocinética , Antineoplásicos/toxicidade , Neoplasias/tratamento farmacológico , Pirazinas/farmacocinética , Pirazinas/toxicidade , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravenosas , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/patologia , Pirazinas/administração & dosagemRESUMO
Twenty-nine patients with advanced pancreatic adenocarcinoma were treated with merbarone, utilizing a daily intravenous schedule for 5 days. Only two partial responses of short duration were observed. The major toxicities were renal, with an increase in creatinine or proteinuria in 17 patients, and mild to moderate nausea and vomiting seen in 22 patients. Merbarone in this dose and schedule has minimal activity in pancreatic cancer.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Tiobarbitúricos/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Indução de Remissão , Tiobarbitúricos/administração & dosagem , Tiobarbitúricos/efeitos adversosRESUMO
Thirty-seven patients with advanced soft tissue sarcoma were treated with merbarone utilizing a daily intravenous schedule for five days. Only one partial response was observed in the thirty-three evaluable patients. The major toxicities were renal, with elevation of creatinine and/or proteinuria, and gastrointestinal, with mild to moderate nausea and vomiting. Merbarone in this dose and schedule has minimal activity in soft tissue sarcoma.
Assuntos
Antineoplásicos/uso terapêutico , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Tiobarbitúricos/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Tiobarbitúricos/administração & dosagem , Tiobarbitúricos/efeitos adversosRESUMO
Hairy cell leukemia is a malignant B-cell disorder characterized by splenomegaly and pancytopenia. The malignant cell is morphologically unique and characterized by fine cytoplasmic projections. Although studies of the cell have revealed important information about its proliferative capacity, cell surface, and membrane composition, less is known about the metabolic characteristics of the cell. We have previously investigated the oxidative metabolism of the hairy cell and have suggested that hairy cells might have a unique glucose metabolism compared to normal lymphocytes. This is indicated by a high rate of [6-14C]glucose oxidation in short-term culture consistent with an active Kreb's cycle and a high ratio of [6-14C]glucose oxidation to [1-14C] glucose oxidation. In this study, we evaluated an additional group of patients with hairy cell leukemia prior to or after treatment with the experimental drug 2'-deoxycoformycin (dCF). We found that in seven of eight patients the leukemic cells had a pattern similar to that previously described and that all of these seven patients had a significant response to therapy. The cells of the eighth patient had minimal Kreb's cycle activity, and at the time of study the patient was resistant to therapy with dCF. The metabolic activity of hairy cells may distinguish them from other lymphoid populations and may be a marker for sensitivity to dCF.
Assuntos
Glucose/metabolismo , Leucemia de Células Pilosas/tratamento farmacológico , Leucemia de Células Pilosas/metabolismo , Pentostatina/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
Our experience suggests a potential role of fludarabine phosphate in the management of hairy cell leukemia. On the basis of this experience, the activity of F-AMP needs to be further evaluated in this disease.