RESUMO
OBJECTIVES: The purpose of this prospective observational study is to evaluate the relation of the comprehensive geriatric assessment (CGA) to tolerability and survival of multi-agent chemotherapy for curative intent in elderly patients with aggressive non-Hodgkin lymphoma (NHL). MATERIALS AND METHODS: Patients who were 1) age ≥65 years, 2) newly diagnosed aggressive NHL, and 3) treated with multi-agent chemotherapy within 2 weeks from the time of diagnosis were enrolled from January 2011 to June 2014. Baseline clinical, laboratory, and CGA data being composed of Mini Nutritional Assessment-Short Form (MNA-SF), Korean version of Mini Mental Status Exam, Korean-Geriatric Depression Scale, and Groningen Frailty Index (GFI), were collected and analyzed for the relation to the outcome factors. RESULTS: Seventy patients were included; the median age was 73.5 years, 27 (38.6%) patients were Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or more, and half of the patients were high or high-intermediate risk by age-adjusted international prognostic index (aaIPI). Most patients received CHOP or CHOP-like chemotherapy. Factors affecting discontinuation of chemotherapy within 12 weeks were poor MNA-SF, poor GFI, poor PS, and presence of B symptom. Among those, poor MNA-SF was independent of other variables in multivariate analysis. Poor MNA-SF, bone marrow involvement, and baseline anemia of hemoglobin<10g /dL were found to be independent factors associated with inferior overall survival whereas aaIPI factors were not. CONCLUSION: MNA-SF predicted tolerability to multi-agents chemotherapy and overall survival in elderly patients with aggressive NHL who were treated with multi-agent chemotherapy.
Assuntos
Avaliação Geriátrica , Linfoma não Hodgkin/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Idoso Fragilizado , Glioxal/uso terapêutico , Humanos , Ifosfamida/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Masculino , Análise Multivariada , Gradação de Tumores , Prednimustina/uso terapêutico , Prednisona/uso terapêutico , Estudos Prospectivos , República da Coreia/epidemiologia , Resultado do Tratamento , Vincristina/uso terapêuticoAssuntos
Idoso , Linfoma/tratamento farmacológico , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Humanos , Linfoma/mortalidade , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Pessoa de Meia-Idade , Mitoxantrona/uso terapêutico , Cuidados Paliativos , Prednimustina/uso terapêutico , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Prognóstico , Vincristina/uso terapêuticoRESUMO
PURPOSE: To evaluate prospectively in patients with follicular lymphoma and a low tumor burden three therapeutic options: delay of any treatment until clinically meaningful progression, immediate treatment with an oral alkylating agent, or treatment with a biologic response modifier, interferon alfa-2b. PATIENTS AND METHODS: Newly diagnosed follicular lymphoma patients with a low tumor burden (n = 193) were randomly assigned to one of three arms: arm 1, no initial treatment (n = 66); arm 2, prednimustine 200 mg/m2/d for 5 days per month for 18 months (n = 64); or arm 3, interferon alfa 5 MU/d for 3 months then 5 MU three times per week for 15 months (n = 63). Clinical characteristics were similar in the three arms. RESULTS: Overall response rates with prednimustine and interferon alfa were 78% and 70%, respectively. The overall response to therapy, when deferred, was similar at 70%. With a median follow-up duration of 45 months after randomization, the median freedom-from-treatment (FFT) interval was 24 months in arm 1 and the interval of freedom from treatment failure (FFTF) was 40 months in arm 2 and 35 months in arm 3. The median overall survival time was not reached and the overall survival rate at 5 years was 78% in arm 1, 70% in arm 2, and 84% in arm 3. Therefore, deferred treatment does not adversely influence survival at 5 years. Patients who progressed within 1 year had a significantly shorter survival duration (median, 48 months). CONCLUSION: Delayed treatment is feasible in patients with follicular lymphoma and a low tumor burden. For patients with early progression, more intensive therapy should be considered. For others, because delay of treatment until significant clinical progression does not seem to hamper the prognosis or subsequent response to treatment, the long-term toxicity of alkylating agents can be reduced.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos Alquilantes/efeitos adversos , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Prednimustina/efeitos adversos , Prednimustina/uso terapêutico , Estudos ProspectivosRESUMO
The authors treated 21 advanced, pretreated Hodgkin's disease patients with CEP (CCNU, etoposide, prednimustine) polychemotherapy between March 1988 and February 1993. Complete remission was achieved in 4 patients, partial remission in 8 patients, while 9 patients were unresponsive to treatment. None of the complete responders relapsed during the follow-up period, and the median duration of remission was 24 months. The median survival for the unresponsive and partially responsive patients was less than half a year. Side-effects included gastrointestinal symptoms, myelosuppression and alopecia, but treatment-related deaths did not occur. The present data confirm the favourable impact of CEP polychemotherapy on pretreated, advanced Hodgkin's disease patients.
Assuntos
Etoposídeo/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Lomustina/uso terapêutico , Prednimustina/uso terapêutico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos Clínicos , Etoposídeo/efeitos adversos , Feminino , Humanos , Lomustina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prednimustina/efeitos adversosRESUMO
Seventy-eight patients with advanced non-Hodgkin's lymphomas were randomized for treatment with prednimustine (Sterecyt) in two different schedules: either receiving continuous treatment at a dosage of 60 mg daily, or intermittent two-week courses with 200 mg daily for five days. The aim of the study was to compare efficacy and side effects of the two different schedules. Forty patients received continuous, and 38 patients intermittent treatment. Objective response was achieved in 66% of 71 evaluable patients, equally distributed between the two treatment arms. The 10-year survival rate was 20% (SE = 6%; continuous treatment) and 11% (SE = 5%; intermittent treatment), respectively (logrank p = 0.26). Median time to response, duration of response and time to progression showed no significant difference between the treatment groups. Median time on treatment was longer for patients treated continuously, probably due to more easily performed dose adjustments in such patients. There was a significant decrease of the white blood cell counts in patients who received prednimustine continuously compared with those treated according to the intermittent schedule (p = 0.02). No significant differences were found regarding the thrombocyte levels. The response rate was closely related to haematological toxicity (p = 0.01). Our results suggest that prednimustine in non-Hodgkin's lymphomas has similar effectiveness both in daily treatment and in a two-weekly intermittent schedule. Continuously given treatment may be easier to govern and, thereby, allow for higher treatment intensity. With respect to toxicity, daily doses of approximately 30-40 mg in previously untreated patients may be recommended.
Assuntos
Linfoma não Hodgkin/tratamento farmacológico , Prednimustina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Prednimustina/efeitos adversos , Prednimustina/uso terapêuticoRESUMO
We observed a decrease in serum bilirubin, alkaline phosphatases (ALP) and IgM in five patients with primary biliary cirrhosis (PBC) treated with Prednimustin (Sterecyt) for 6 months. In contrast to pretreatment findings, C3 activation was undetectable during treatment in three patients where normalization of serum IgM was achieved. After discontinuation of Prednimustin, bilirubin and ALP levels rapidly returned to pretreatment values, although IgM remained normal for up to 6 months in some patients. We conclude that Prednimustin might be of value in patients with symptomatic PBC where liver transplantation is not an option, and that it should be evaluated in a controlled study. However, the rapid reactivation of the disease after conclusion of treatment must be considered.
Assuntos
Cirrose Hepática Biliar/tratamento farmacológico , Prednimustina/uso terapêutico , Idoso , Feminino , Humanos , Imunoglobulina M/sangue , Cirrose Hepática Biliar/imunologia , Cirrose Hepática Biliar/fisiopatologia , Testes de Função Hepática , Masculino , Pessoa de Meia-IdadeRESUMO
Thirty-five patients with a mean age of 60.6 years (44-78 years, 22 male, 13 female) with advanced low-grade non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), or prolymphocytic leukemia (PLL) were treated every 4 weeks with prednimustine 100 mg/m2 p.o. d 1-d 5 and mitoxantrone 8 mg/m2 i.v. d 1 and d 2. Seven patients had CLL, one lymphocytic NHL, two PLL, 13 immunocytoma, nine centroblastic/centrocytic NHL, and three centrocytic NHL. Twenty-five patients were pretreated. The subjective toxicity of the treatment was mild, with no WHO grade-3 alopecia, polyneuropathy, cardiotoxicity, mucositis, nausea, or vomiting. Hematologic side effects with WHO grade-4 granulopenia and thrombopenia were experienced by 26% and 23% of the patients, respectively. The overall response rate (CR+PR) was 72% for lymphoma patients and 37% for CLL patients, with a median remission duration of 14.6 months. The maximum response was achieved after a median of two treatment courses. Prednimustine with mitoxantrone is a subjectively well tolerated treatment for low-grade malignant NHL, to be further evaluated in phase-III studies. The regimen may shorten the duration of treatment, saving time-consuming out-patient visits and costs.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Promielocítica Aguda/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Mitoxantrona/uso terapêutico , Prednimustina/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/toxicidade , Prednimustina/toxicidadeRESUMO
The pharmacokinetics of chlorambucil, phenylacetic acid mustard (the beta-oxidation product of chlorambucil), and prednisolone were investigated in a cross-over study after oral administration of chlorambucil (30 mg) + prednisolone (50 mg) versus prednimustine (300 mg), the ester of chlorambucil and prednisolone. Intact prednimustine could not be detected in plasma at any time. After administration of prednimustine, the plasma concentration-time curves of chlorambucil, phenylacetic acid mustard, and prednisolone showed a retarded profile compared to the administration of the single components. The mean bioavailability was 14% for chlorambucil, 21% for phenylacetic acid mustard, and 22% for prednisolone, when given as prednimustine, compared to the administration of free compounds in stoichiometrically equivalent doses. When given in the oral dosages mentioned above, the average dose-intensity was 62% for chlorambucil, 95% for phenylacetic acid mustard, and 72% for prednisolone, indicating sufficient therapeutic concentrations of the detectable agents.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias da Mama/tratamento farmacológico , Clorambucila/farmacocinética , Linfoma não Hodgkin/tratamento farmacológico , Prednimustina/farmacocinética , Prednisolona/farmacocinética , Administração Oral , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Clorambucila/administração & dosagem , Clorambucila/uso terapêutico , Feminino , Humanos , Linfoma não Hodgkin/sangue , Masculino , Taxa de Depuração Metabólica , Prednimustina/administração & dosagem , Prednimustina/uso terapêutico , Prednisolona/administração & dosagem , Fatores de TempoRESUMO
Prednimustine (Stereocyt, Leo 1031) is a chlorambucil ester of prednisolone. Results from clinical trials confirm that prednimustine is active in malignant lymphomas. The efficacy of Stereocyt was evaluated in 25 patients, who were divided into three subgroups: 10 patients with refractory Hodgkin's disease and 7 with refractory non-Hodgkin lymphoma (NHL), while 8 patients received prednimustine as primary therapy for low-grade NHL. Totally 17 partial remissions were observed in all three groups of patients. Leukopenia and thrombopenia were induced in 3 patients, but were mild and reversible after withdrawal of the drug.
Assuntos
Clorambucila/análogos & derivados , Doença de Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Prednimustina/uso terapêutico , Adulto , Idoso , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de RemissãoRESUMO
A total of 76 patients with advanced epithelial ovarian carcinoma were randomised to receive 6 months of treatment with either a combination of hexamethylmelamine, 5-fluorouracil, cisplatin and prednimustine or prednimustine alone following initial surgery. Pathologically confirmed response rates were 35% for combination chemotherapy and 28% for prednimustine, and the overall survival was identical for the two groups. Seven patients achieved a pathologically defined complete response, one of whom relapsed at 8 months; the others remain disease-free 18-36 months (median, 23 months) after presentation. The extent of initial surgery significantly affected the survival of patients receiving prednimustine but not of those receiving combination chemotherapy. Prednimustine can produce durable responses in advanced ovarian cancer using a schedule that results in negligible toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Clorambucila/análogos & derivados , Neoplasias Ovarianas/tratamento farmacológico , Prednimustina/uso terapêutico , Altretamine/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Laparotomia , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Prednimustina/efeitos adversos , Prognóstico , Distribuição AleatóriaRESUMO
Thirty patients with advanced and mainly pretreated breast cancer were treated with a combination of premarin, prednimustine, high-dose folinic acid and 5-fluorouracil. Among the 30 evaluable patients, 9 (30%) achieved an objective response (median duration: 9 months). Oral mucositis was the limiting toxicity, while myelosuppression was quite mild. In spite of considerable activity as salvage regimen, these results do not seem better than those achieved in our Institute with high-dose folinic acid and 5-fluorouracil alone.
Assuntos
Clorambucila/análogos & derivados , Estrogênios Conjugados (USP)/uso terapêutico , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Prednimustina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Leucovorina/administração & dosagemAssuntos
Clorambucila/análogos & derivados , Estradiol/análogos & derivados , Neoplasias/tratamento farmacológico , Administração Oral , Anticorpos Monoclonais/uso terapêutico , Clorambucila/administração & dosagem , Clorambucila/efeitos adversos , Clorambucila/uso terapêutico , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Estradiol/uso terapêutico , Estramustina/uso terapêutico , Humanos , Prednimustina/uso terapêutico , Receptores de Superfície CelularRESUMO
A phase II study of Prednimustine (PMN) was conducted for follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). PMN at a dose of 40-60 mg/body, p.o. every day, was administered to 17 patients with FL and 4 with CLL. The dose and schedule of PMN was modified according to hematological toxicity. Among the 17 patients with FL, there were 6 (35.3%) CRs and 7 (41.2%) PRs, with a high response rate of 76.5%. Among the 4 patients with CLL, there were 2 PRs and one case which showed clinical improvement. PMN was effective for cases of FL and CLL refractory to alkylating agents, and therefore the result suggested a lack of clinical cross-resistance to these agents. As to the side effects observed in patients with FL, mild leukopenia (median of lowest count 3,150/mm3) occurred. One case experienced anorexia, while increased appetite was observed in 4 cases. We conclude that PMN is effective for FL and CLL, and that in addition, it has an advantage in that its mild side effects allow long-term administration through outpatient clinics, so that the quality of life for patients is not impaired.
Assuntos
Clorambucila/análogos & derivados , Leucemia Linfoide/tratamento farmacológico , Linfoma Folicular/tratamento farmacológico , Prednimustina/uso terapêutico , Administração Oral , Adulto , Idoso , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednimustina/administração & dosagemRESUMO
Twenty-one patients with refractory chronic lymphocytic leukemia (CLL) were entered into this Northern California Oncology Group (NCOG) study of prednimustine, an ester of chlorambucil and prednisolone. All patients had active disease and were refractory to standard alkylating agent chemotherapy. Treatment consisted of prednimustine 100 mg/m2/day orally for 3 consecutive days every 2 weeks. By strict response criteria used in this study there was one complete remission (CR), no partial remissions (PR), and three cases of clinical improvement (CI) in 18 evaluable patients, for a total response rate of 22%. The median duration of response is 20+ months, with two patients continuing to respond. Toxicity of this intermittent prednimustine regimen consisted primarily of mild to moderate thrombocytopenia and neutropenia. No episodes of treatment-associated infection or hemorrhage occurred, and nonhematologic toxicity was minor. Using strict response criteria, this study fails to confirm previous reports of high response rates for prednimustine in patients with CLL refractory to standard therapy. The significance of the response category of clinical improvement in CLL is demonstrated by the substantial improvement in objective parameters and the long duration of response. This study also emphasizes the need for standardization of response criteria for this disease.
Assuntos
Clorambucila/análogos & derivados , Leucemia Linfoide/tratamento farmacológico , Prednimustina/uso terapêutico , Alquilantes/uso terapêutico , Humanos , Pessoa de Meia-IdadeRESUMO
Starting in February 1980, 58 patients with Hodgkin's disease refractory to both MOPP and ABVD received as third-line chemotherapy a combination of CCNU or lomustine, etoposide, and prednimustine (CEP). Complete response (CR) was achieved in 40% of cases and partial response (PR) in 14%. The median duration of CR was greater than 15 months, and the median survival of complete responders was longer than 24 months. In addition, CEP alternating with ABVD was given to 21 patients refractory to MOPP chemotherapy. In this series, CR was documented in 67% of patients with a median duration of 24+ months and a median survival of 36+ months. Treatment was generally well tolerated, and all acute side effects were reversible. Present findings indicate that CEP is an effective regimen in patients refractory to MOPP and ABVD.