ABSTRACT
We performed a controlled clinical trial to define the use of a brief therapy: CMED (cyclophosphamide, etoposide, methotrexate, and dexamethasone) compared with standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in the treatment of peripheral T-cell lymphoma unspecific (PTCLu). The end point to the study was to assess efficacy, measured from complete response rate (CRR), progression-free survival (PFS), and overall survival in 217 previously untreated patients with PTCLu. In an intent-to treat analysis all patients were evaluable. CRR was 76% in CMED regimen and 57% in CHOP arm (P<0.05); actuarial curves at 10 years showed that PFS was 70% and 43%, respectively (P<0.01); overall survival was 60% and 34%, respectively (P<0.01). Adjuvant radiotherapy was employed in 48 cases (54% of patients who achieve CR in CMED arm) and 30 patients (47% of patients who achieve CR in CHOP arm). Acute toxicity was mild and well tolerated. Our results showed that the CMED regimen is feasible and effective in PTCLu.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, T-Cell, Peripheral/drug therapy , Adult , Aged , Cyclophosphamide/therapeutic use , Dexamethasone/therapeutic use , Disease-Free Survival , Doxorubicin/therapeutic use , Etoposide/therapeutic use , Female , Humans , Lymphoma, T-Cell, Peripheral/diagnosis , Lymphoma, T-Cell, Peripheral/mortality , Lymphoma, T-Cell, Peripheral/pathology , Male , Methotrexate/therapeutic use , Middle Aged , Neoplasm Staging , Prednisone/therapeutic use , Prognosis , Vincristine/therapeutic use , Young AdultABSTRACT
To assess efficacy and toxicity of rituximab and dose chemotherapy in high-risk diffuse large cell lymphoma, we conducted a controlled clinical trial to assess efficacy and toxicity of a dose-dense regimen CEOP- 14 (cyclophosphamide, epirubicin, vincristine, and prednisone every 14 d) compared to CEOP-14 plus rituximab. One hundred and ninety-six patients were randomized to received CEOP-rituximab (cyclophosphamide 1500 mg/m2, epirubicin 120 mg/m2, vincristine, and prednisone at standard dose and rituximab at 375 mg/m2) compared with the same chemotherapy administered every 14 d (CEOP-14). In an intent-to-treat analysis all patients were available for efficacy and toxicity. Complete response in CEOP-14 was observed in 73 cases (74%) and in 75 patients (76%) in the CEOP-R regimen (76%) (p = 0.8). With a median follow-up of 53.4 mo, median has not been reached in time to tumor-progression (TTP) and overall survival (OS). Actuarial curves at 5 yr showed that TTP and OS in patients treated with CEOP-R were 74% and 67%, respectively, that were not statistical different when compared to CEOP-14, 72% and 65%, respectively (p = 0.8). Acute toxicity was mild and well tolerated. The use of a dense-dose regimen is useful and well tolerated in patients with very high risk diffuse large cell lymphoma. The addition of rituximab did not improve outcome in these setting of patients.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Adult , Aged , Antibodies, Monoclonal, Murine-Derived , Cyclophosphamide/therapeutic use , Dose-Response Relationship, Drug , Epirubicin/therapeutic use , Female , Humans , Male , Middle Aged , Prednisone/therapeutic use , Rituximab , Survival Rate , Treatment Outcome , Vincristine/therapeutic useABSTRACT
Residual disease in patients with diffuse large B-cell lymphoma after intensive chemotherapy remains a problem. Radiotherapy has been used in some retrospective studies without definitive conclusions. We report the first controlled clinical trial to define the role of radiotherapy in this setting of patients. One hundred and sixty-six patients with diagnosis of diffuse large B-cell lymphoma, high- or high-intermediate clinical risk, with residual disease (defined as tumor mass < 5 cm) were randomly assigned to received radiotherapy at the involved field, with 30 Gy delivered in 20 sessions or no radiation (control group). Median follow-up was 135 mo; patients who received radiotherapy have an better outcome. Actuarial curves at 10 yr showed that progressive-free disease was 86% and overall survival was 89%; those were statistical significant when compared to patients who did no received radiotherapy: 32% and 58% respectively, (p < 0.001). Toxicity was mild and well tolerated. We concluded that presence of residual mass after chemotherapy in patients with aggressive malignant lymphoma has a worse prognosis, and salvage radiotherapy improves outcome with mild toxicity. We feel that radiotherapy will be considered as necessary treatment in this special group of patients.
Subject(s)
Lymphoma, B-Cell/radiotherapy , Lymphoma, Large B-Cell, Diffuse/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide , Doxorubicin , Female , Humans , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/pathology , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Middle Aged , Neoplasm, Residual/radiotherapy , Prednisolone , Prognosis , Survival Analysis , Survival Rate , VincristineABSTRACT
Treatment in patients with multiple myeloma remain to be defined. Younger patients (defined as a cut-off level < 65 years old) will be treated with chemotherapy and transplant procedures. However, most patients > 65 years old are not candidates for this therapeutic approach and the use of intensive chemotherapy could be associated to severe toxicity. We developed an new, not-cytotoxic regimen with dexamethasone 30 mg/m(2), iv, days 1 to 4, all trans retinoic acid 45 mg/m(2), po, days 5 to 14 and interferon alfa 2a 4.5 MU, sc, daily, days 5 to 14 (DAI regimen) administered every 28 days in number of 6 cycles, at this point patients were restaging, if they showed complete response, objective response or partial response they were conducted to received thalidomide 100-200 mg po, daily and dexamethasone 10 mg/2, po days 1 to 4 at monthly intervals, for 18 months. Forty one patients were enrolled in an Phase II study. In an intent to treat analysis all patients were evaluable. Complete response was observed in 18 cases (43%), objective response in 10 patients (24%) and partial response in 5 patients (12%), overall response rate was 80%. Eight patients were considered failures. At an median of 36 months, no relapse of progression disease has been observed, thus actuarial curves at 3-years showed that event free survival is 100% and overall survival is 91%. Toxicity was mild, all patients received the planned dose in time. This regimen appear to be useful in older patients with multiple myeloma, the response rate is higher and toxicity was mild. Controlled clinical trials comparing with conventional chemotherapy will be conducted to define the role of this therapeutic approach.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Multiple Myeloma/drug therapy , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Disease-Free Survival , Female , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Interferon alpha-2 , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Male , Multiple Myeloma/radiotherapy , Recombinant Proteins , Thalidomide/administration & dosage , Thalidomide/adverse effects , Tretinoin/administration & dosage , Tretinoin/adverse effectsABSTRACT
Anthracyclines are a group of drugs that are useful in the treatment of Hodgkin's disease, but have been associated with severe, and in some cases lethal, cardiac toxicity. Apparently, cardiac toxicity is more frequent after 10 years of anthracycline therapy, but no longer studies of cardiac toxicity have been reported. Four hundred and seventy-six patients with Hodgkin's disease, stages III and IV, were randomly assigned to receive ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) compared with EBVD (epirubicin instead of doxorubicin) and MBVD (mitoxantrone instead of doxorubicin) at standard doses. The endpoint was the presence of a clinical cardiac event (CCE) or abnormalities in equilibrium radionuclide angiocardiography (ERNA) and echocardiogram. The patients did not receive radiation therapy and when relapsed they were censored from cardiac toxicity. The median follow-up was 11.5 years (range 7.5 - 14.8 years). CCE was observed in 17% in the MBVD arm, 9% in the ABVD arm and 6% in the EBVD arm (P < 0.001). Mortality associated with CCE was 12% with MBVD, 7% with ABVD and 2% with EBVD. Abnormalities in ERNA and echocardiogram were observed 6 - 36 months before the presence of a CCE. An excess in the standard mortality ratio was observed with the 3 regimens when compared with the general population: 19.4 for EBVD, 46.0 for ABVD and 67.8 for MBVD, which was confirmed with an increase in absolute excess risk/10,000 person-years of 15.6, 39.0 and 58.7, respectively. Overall survival was better in patients treated with EBVD because less cardiac events were observed. The use of mitoxantrone was associated with a high rate of relapse and cardiac events. Thus, we would not recommend use of the drug in Hodgkin's disease. ERNA and echocardiogram are early detection tests for cardiac toxicity and can be employed in surveillance studies.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Heart Diseases/chemically induced , Heart/drug effects , Hodgkin Disease/drug therapy , Mitoxantrone/adverse effects , Adolescent , Adult , Bleomycin/adverse effects , Dacarbazine/adverse effects , Disease-Free Survival , Doxorubicin/adverse effects , Echocardiography , Epirubicin/adverse effects , Female , Gated Blood-Pool Imaging , Heart Diseases/diagnosis , Hodgkin Disease/complications , Hodgkin Disease/pathology , Humans , Male , Middle Aged , Neoplasm Staging , Remission Induction , Survival Rate , Treatment Outcome , Vinblastine/adverse effectsABSTRACT
Treatment of patients with early stage gastric mucosa-associated lymphoid tissue (MALT) remains undefined. We began a controlled clinical trial to evaluate efficacy and toxicity of the most common therapies. Two hundred and forty-one patients with gastric low-grade MALT lymphoma in early stage (IE and IIE) were randomized to surgery (80 cases), radiotherapy (78 cases), and chemotherapy (83 cases). With a median follow-up of 7.5 yr, actuarial curves at 10 yr showed that event-free survival was 52% in patients treated with surgery, 52% in radiotherapy arm, and 87% in the chemotherapy group (p < 0.01). However, overall survival did not showed any statistical differences: 80%, 75% and 87%, respectively (p = 0.4). Acute and late toxicities were mild. No death-related treatments were observed. No clear differences were observed between the most common therapies in patients with primary gastric MALT lymphoma in early stages, probably because this type of lymphoma has an high response rate to salvage treatment after failure to local treatment (surgery and radiotherapy). Thus considered, chemotherapy alone is an effective and safe therapeutic approach in this setting of patients. Surgery or radiotherapy will be reserved to patients that are not candidates for chemotherapy.
Subject(s)
Lymphoma, B-Cell, Marginal Zone/therapy , Stomach Neoplasms/therapy , Adult , Aged , Antineoplastic Agents/adverse effects , Female , Humans , Lymphoma, B-Cell, Marginal Zone/mortality , Male , Middle Aged , Postoperative Complications/etiology , Radiotherapy/adverse effects , Stomach Neoplasms/mortalityABSTRACT
The aim of the present study was to evaluate an intensive chemotherapy regimen in patients with diffuse large B-cell lymphoma and poor prognosis, as presence of high- or high-intermediate clinical risk, bulky disease, high levels of beta 2 microgloblin, and more than two extranodal sites of involvement at diagnosis. One hundred previously untreated patients were treated with an intensive CEOP-Bleo regimen with increased doses of cyclophosphamide (1000 mg/m(2)) and epirubicin (120 mg/m(2)) in each cycle. Granulocyte colony-stimulating factors was employed to ameliorate severe granulocytopenia. Complete response was achieved in 79 cases (79%). With a median follow-up of 32.3 mo (range 10-45 mo) only seven patients have relapsed. Thus, actuarial curves at 3 yr, showed that event-free survival was 72%. Five died secondary to tumor progression, actuarial curves at 3-yr for overall survival were 75%. Toxicity was mild, granulocytopenia grade III or IV were observed in the 46% of the cycles; infection-related granulocytopenia was observed in 17%, but no fatality due to therapy was observed. Cardiac toxicity was mild, only seven patients showed a drop in left ejection ventricular function, but no symptomatic heart failure has been observed. The intensive CEOP-Bleo regimen with increasing doses of cyclophosphamide and epirubicin is a useful and well-tolerated regimen in the treatment of poor prognosis diffuse large B-cell lymphoma.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, B-Cell/drug therapy , Adult , Aged , Antibiotics, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bleomycin/administration & dosage , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Epirubicin/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma, B-Cell/mortality , Male , Middle Aged , Prednisone/administration & dosage , Prednisone/therapeutic use , Prognosis , Risk Factors , Survival Analysis , Time Factors , Treatment Outcome , Vincristine/administration & dosage , Vincristine/therapeutic useABSTRACT
The role of adjuvant radiotherapy to sites of nodal bulky disease in patients with aggressive diffuse large cell lymphoma (DLCL), and stage IV remain undefined. We began a prospective controlled clinical trial to evaluate impact in event free survival (EFS) and overall survival (OS) in a large cohort of patients with a longer follow-up. Between 1989 and 1995; 341 patients with aggressive DLCL and presence of nodal bulky disease (tumor mass > 10 cm) in pathological proven complete response after intensive chemotherapy were randomized to received either radiotherapy (involved fields, 40 Gy) or not. The 5-year EFS and OS in radiated patients were respectively: 82% (95% Confidence interval (CI): 70-89%) and 87% (95% 80-99%), that were statistically significant to control group: 55% (41-64%) (P < 0.001) and 66% (95% CI: 51-73%) (P < 0.01) respectively. Radiotherapy was well tolerated, acute toxicity was mild and until now late toxicity did not appear. The use of adjuvant radiotherapy improve EFS and OS and probably the possibility of cure in patients diffuse large cell lymphoma with worse prognostic factors. Thus, we felt that adjuvant radiotherapy will be considered as part of the initial treatment in this setting of patients.
Subject(s)
Lymphoma, Large B-Cell, Diffuse/radiotherapy , Radiotherapy, Adjuvant , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Disease-Free Survival , Epirubicin/administration & dosage , Female , Follow-Up Studies , Humans , Life Tables , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Male , Mexico , Middle Aged , Neoplasm Staging , Prednisone/administration & dosage , Prospective Studies , Radiotherapy, Adjuvant/statistics & numerical data , Survival Analysis , Treatment Outcome , Vincristine/administration & dosageABSTRACT
Maintenance therapy in patients with aggressive malignant lymphoma using biological modifiers remains uncertain. We conducted a controlled clinical trial to evaluate the efficacy and toxicity of interferon-alpha 2b, cyclophosphamide, and prednisone as maintenance therapy in patients with aggressive diffuse large B cell lymphomas in complete remission after aggressive chemotherapy. In an intent-to-treat analysis, 169 patients were eligible for this study; the end points were event-free survival (EFS) and overall survival (OS). With a median follow-up of 49.3 months, no statistical differences were observed and actuarial curves at 5 years showed that EFS was 71% (95% confidence interval [CI], 63-79%) for patients who received maintenance compared to 63% (95% CI, 59-71%) for patients in control group (p = 0.05). No statistical differences were observed in OS between maintenance arm: 84% (95% CI, 78-89%) and control group 83% (95% CI, 77-88%) in control group (p = 0.2). All patients received the maintenance therapy as planned and in time, thus dose intensity was considered 1.0 in all cases. Acute toxicity was mild, and no delay or suspension of treatment was necessary. Late toxicity was not evident until now. We conclude that use of maintenance therapy combining interferon-alpha 2b, cyclophosphamide, and prednisone is not useful in patients with aggressive lymphoma if they had been treated with aggressive combined chemotherapy.
Subject(s)
Cyclophosphamide/therapeutic use , Interferon-alpha/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Prednisone/therapeutic use , Adult , Aged , Cyclophosphamide/adverse effects , Disease-Free Survival , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Male , Middle Aged , Prednisone/adverse effects , Recombinant ProteinsABSTRACT
We start a controlled clinical trial to assess efficacy and toxicity of EBVD (epirubicin, bleomycin, vinblastine and dacarbazine) with an intensive and brief program of seven drugs administered weekly for 12 weeks in previously untreated patients with advanced Hodgkin's disease. Two hundred and sixty four patients were randomized to receive EBVD chemotherapy (134 cases) or intensive chemotherapy (130 cases). Eligible patients were either previously untreated stages III or IV. Patients with bulky disease received adjuvant radiotherapy. In an intent to treat analysis, all patients were evaluable for efficacy and toxicity. Complete response rate to the two regimens were similar (88 and 84%, respectively). However, actuarial 5 years overall survival rates were 87% (95% confidence interval (CI): 78-94%) for the EBVD regimen, which is statistically different to 59% (95% CI: 48-66%) for the intensive program (p < 0.01). Event-free survival were 83% (95% CI: 74-89%) for EBVD and 65% (95% CI: 58-71%) for the intensive program (p < 0.01). Significantly, more episodes of granulocytopenia grade III-IV, infection-related granulocytopenia, death-related infection even early hematological support with granulocyte colony stimulating factor were seen with the intensive, program. In the present single center trial, intensive chemotherapy did not appear to have better results when compared with standard chemotherapy in patients with advanced Hodgkin's disease.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Actuarial Analysis , Adult , Aged , Agranulocytosis/chemically induced , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/toxicity , Bleomycin/administration & dosage , Dacarbazine/administration & dosage , Epirubicin/administration & dosage , Female , Hodgkin Disease/complications , Hodgkin Disease/mortality , Humans , Infections/chemically induced , Male , Middle Aged , Survival Analysis , Treatment Outcome , Vinblastine/administration & dosageABSTRACT
OBJECTIVES: We evaluate the long-term results of a randomized clinical trial in patients with advanced stages (III and IV) of follicular lymphoma using chemotherapy or combined therapy (chemotherapy following by adjuvant radiotherapy in patients with nodal bulky disease). MATERIAL AND METHODS: Between 1981 and 1995, patients with follicular lymphoma were treated with combined chemotherapy, mostly anthracycline-based regimens; patients who achieved complete response were randomly assigned either to receive adjuvant radiotherapy to sites or to nodal bulky disease or not (control group). RESULTS: Four hundred and sixty-nine patients were randomized; in an intent-to-treat analysis all were evaluable for efficacy and toxicity. Actuarial curves at 20yr showed that event-free survival (EFS) and overall survival (OS) in the control group were 41% [95% confidence interval (CI) 36-56%) and 71% (95% CI 65-78%), respectively; these were statistically different from results for the patients who received adjuvant radiotherapy: 68% (95% CI 62-72%) and 89% (95% CI 79-96%), respectively (P<0.01). Acute and late toxicity were minimal; only four patients (<1%) developed myelodysplastic syndrome/acute leukemia. Cardiac toxicity was 2%, but one case was lethal. Thirty-six patients (8%) died secondary to unrelated causes, in complete remission. CONCLUSIONS: The use of adjuvant radiotherapy in patients with poor-prognosis follicular lymphoma increases EFS and OS with minimal toxicity. We feel that follicular lymphoma should be treated curatively because <80% of patients will be in first complete response at <20yr. The use of adjuvant radiotherapy will be considered in the first line of treatment in this set of patients.
Subject(s)
Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/radiotherapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cause of Death , Combined Modality Therapy , Disease-Free Survival , Female , Heart Diseases/chemically induced , Humans , Lymphoma, Follicular/mortality , Male , Middle Aged , Myocardial Infarction/chemically induced , Neoplasm Staging , Prognosis , Recurrence , Remission Induction , Survival RateABSTRACT
Anthracyclines remain as the best drugs in the treatment of patients with aggressive malignant lymphoma in combination with other cytotoxic drugs. However, dose escalation is poorly tolerated and acute and late cardiac toxicity has limited the use of these compounds. Pegylated liposomal doxorubicin has been proven to be useful in some malignancies, without the presence of acute cardiac toxicity and with a good response rate in patients with relapsed/refractory lymphomas. We report the first study of this drug in combination chemotherapy in patients with previously untreated aggressive malignant lymphoma. Twenty consecutive patients with diagnosis of diffuse large-B-cell lymphoma, age < 18 yr to < 70 yr, without previous treatment, HIV-negative high and high-intermediate clinical risks were treated with the CHOP-Bleo regimen at standard doses, using pegylated-liposomal doxorubicin instead of doxorubicin, at 25 mg/m2 (3 patients), 30 mg/m2 (3 patients), and 35 mg/m2 (14 patients). Complete response was achieved in 17 cases (85%), with failure in 3 patients (15%). At a median follow-up of 18.1 mo, relapse has not been observed. Two patients died secondary to tumor progression. Toxicity was mild, only three episodes of granulocytopenia grade I were observed, and no mucositis, thrombocytopenia, or granulocitopenia grade > 2 was observed. Erythrodisestesias grade II was observed in one case and grade I in two cases. Cardiac function was normal before and 12 mo after chemotherapy. Pegylated liposomal doxorubicin appear as an promising drug in the treatment of patients with aggressive malignant lymphoma.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/therapeutic use , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Lymphoma, B-Cell/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Prednisone/therapeutic use , Vincristine/therapeutic use , Adult , Female , Humans , Infusions, Intravenous , Liposomes , Male , Middle Aged , Pilot Projects , Polyethylene GlycolsABSTRACT
A controlled clinical trial evaluated the usefulness of three different therapeutic approaches in the treatment of spinal cord compression (SCC) as primary manifestation of malignant lymphoma with the following end-points: neurological function, event free survival (EFS) and overall survival (OS). Forty-eight patients with SCC as unique manifestation (IE) of malignant lymphoma, were randomly assigned to receive either: radiotherapy (16 patients), chemotherapy (11 patients) or combined therapy (radiotherapy followed by chemotherapy, 21 patients). Although neurological recovery was similar in both groups, EFS and OS were better in the combined therapy arm. Actuarial curves at 10 years showed that EFS was 50% for patients treated with radiotherapy, 46% in the chemotherapy arm and 76% in the combined therapy group. Overall survival was 58, 38 and 76%, respectively, however because of the small number of patients, no statistical differences were observed. Although malignant lymphoma with SCC as primary manifestation could be considered as a localized disease, more patients could have microscopic disseminated disease. The use of combined therapy improves the outcome in this group of patients, and so it should be considered the treatment of choice.
Subject(s)
Lymphoma/complications , Spinal Cord Compression/drug therapy , Spinal Cord Compression/radiotherapy , Actuarial Analysis , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Longitudinal Studies , Lymphoma/therapy , Male , Middle Aged , Nervous System Diseases/etiology , Nervous System Diseases/therapy , Spinal Cord Compression/etiology , Survival Rate , Treatment OutcomeABSTRACT
To determine if the use of adjuvant radiotherapy to sites of initial bulky disease and adequate modern chemotherapy in patients with advanced stages (IIIB and IV) Hodgkin's disease could improve duration of remission and overall survival. Patients previously untreated with pathologically documented advanced stages Hodgkin's disease were randomly assigned to received chemotherapy alone with EBVD regimen (epirubicin, bleomycin, vinblastine and dacarbazine): 56 patients or combined therapy: The same chemotherapy regimen following by adjuvant radiotherapy (35 Gy) to sites of initial bulky disease (tumor mass >7 cm diamenter): 54 patients. Five year overall survival rates were 88% (48 patients) and 60% (34 patients) from combined therapy compared to chemotherapy alone respectively (p < 01) (95% confidence interval (CI): for the difference 18% to 39%). Five-year failure free survival were 83% and 50% respectively (p < 01) (95% CI for difference: 22% to 35%). Toxicity was moderate and well tolerate. No death-related treatment were observed. After a median follow-up of 66 months, no second solid neoplasmas or acute leukemia has been observed. The use of adjuvant radiotherapy to sites of initial bulky disease following the use of modern chemotherapy in patients with advanced stages Hodgkin's disease improve outcome with increase in failure free survival and overall survival, with moderate toxicity. More randomized clinical trials are warranted to define this therapeutic approach.
ABSTRACT
Teinta y cinco pacientes que tuvieron criterios de mieloma múltiple refractario (MMR) fueron seleccionados para un estudio clínico con el fin de comparar la eficacia de la combinación epirubicina, vincristina y dexametasona (EVD) comparándola con la combinación de mitoxantrona, vincristina y dexametosona (MVD). No se observaron diferencias significativas entre los dos grupos en relación a los factores pretratamiento. Once de los 18 pacientes (61 por ciento) tratados con el régimen EVD tuvieron algún tipo de respuesta, mientras que sólo seis de los 17 pacientes (35 por ciento) en el grupo MVD tuvieron respuesta. La duración de la respuesta fue mejorando en el grupo tratando con el régimen EVD (16 meses) que con el régimen MVD (7 meses). Así mismo, la duración de la supervivencia fue significativamente mayor a los que recibieron la combinación de EVD que en aquellos que recibieron el MVD 24 y 11 meses, respectivamente. La toxicidad fue moderada en ambos grupos de tratamiento y no se observaron muertes relacionadas con el tratamiento en alguno de los dos grupos. Con base en los resultados de este pequeño grupo de enfermos, se puede considerar que la administración de epirubicina en combinación con otros citotóxicos es útil en pacientes con MMR, ya que se puede observar un buen número de respuestas, con moderados efectos tóxicos. Por el contrario, no pudimos corroborar la utilidad de la mitoxantrona en combinación con otros citotóxicos y probablemente es un medicamento que deba ser considerado como de segunda línea en el tratamiento de casos con MMR
Subject(s)
Radiotherapy , Spinal Cord Neoplasms/therapy , Vincristine/pharmacokinetics , Dexamethasone/pharmacokinetics , Doxorubicin/therapeutic use , Mitoxantrone/pharmacokinetics , Multiple Myeloma/therapyABSTRACT
Con el fin de evaluar el papel de la radioterapia, usada como primer intento curativo en pacientes con enfermedad de Hodgkin en estadio temprano, se efectuó un análisis retrospectivo de 86 pacientes en los cuales se usó radioterapia ganglionar total (RGT) como enfoque terapéutico primario. El grupo tiene un seguimiento de 13.1 años como mediana y la duración de la supervivencia fue el punto más importante en el presente análisis. El 60 porciento de los pacientes con estadio IA permanecen en primera remisión, mientras que sólo el 39 porciento de los casos en estadio IIA están en dicha condición (p<.01). La mediana de la supervivencia a 10 años también fue significativamente diferente: 78 porciento para los pacientes en estadio IA comparado con el 55 porciento para los casos en estadio IIA (p<.01). En el análisis de los factores pronósticos se encontró que la presencia de estadio IIA y enfermedad voluminosa (adenomegalia > 7 cm) fueron asociados a un mal pronóstico. Se puede considerar que la RGT sólo puede considerarse como curativa en los pacientes en estadio IA de la enfermedad de Hodgkin, pero siempre y cuando no tengan enfermedad voluminosa.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Homeopathic Clinical-Dynamic Prognosis , Hodgkin Disease/radiotherapy , Radiotherapy/statistics & numerical data , PrognosisABSTRACT
La beta 2 microglobulina es una proteína de bajo peso molecular relacionada con el sistema HL-A, que se encuentra virtualmente en todas las células nucleadas. En pacientes con mieloma múltiple (MM) se ha encontrado que niveles elevados de esta proteína se asocian con un pobre pronóstico tanto para obtener respuesta terapéutica como en la duración de la supervivencia. Con el fin de determinar la importancia de la misma, en 70 pacientes con MM sin tratamiento previo, se determinaron niveles séricos de beta 2 microglobulina y se efectuó un análisis multivariable con otros factores pronósticos. Se encontró que los factores asociados a un mal pronóstico en pacientes con MM fueron niveles elevados de beta 2 microglobulina y estadio, independientemente de otros factores analizados, ya que la supervivencia fue significativamente mejor: 80 porciento a 5 años del grupo de pacientes con estadio I y niveles normales de beta 2 microglobulina, cuando se compara con pacientes en estadio III y niveles elevados de beta 2 microglobulina (> 8.0 *g/mL) en las que todos los pacientes estaban muertos a los 27 meses del diagnóstico. Se puede considerar que los niveles séricos de beta 2 microglobulina son un indicador de mal pronóstico en pacientes con MM y que su determinación debe hacerse como parte fundamental del estudio inicial de estos pacientes.
Subject(s)
Humans , Male , Female , Middle Aged , beta 2-Microglobulin/analysis , Multiple Myeloma/blood , Mexico , Multiple Myeloma/mortality , Prognosis , Survival AnalysisABSTRACT
En un estudio clínico prospectivo noventa y ocho pacientes con linfoma maligno y sin tratamiento previo fueron divididos al azar, un grupo recibió quimioterapia con: ciclofosfamida, hidroxidauniladriamician, vincristina, prednisona y bleomicina (CHOP-Bleo); mientras que otro grupo recibió dos ciclos de pre-inducción con dosis bajas de metotrexato, seguida del mismo tipo de quimioterapia: CHOP-Bleo. El número de pacientes con muerte temprana fue menor en el grupo que fue tratado con la pre-inducción; asimismo, en este grupo hubo más pacientes que obtuvieron la remisión completa, mayor duración de la misma y de supervivencia. La toxicidad con el regimen de pre-inducción fue aceptable, mientras que la secundaria a quimioterapia convencional (CHOP-Bleo) fue semejante en ambos grupos. Con base en estos resultados se considera que el uso de dosis bajas de metotrexato como tratamiento de pre-inducción en pacientes con linfoma maligno es útil y benéfico, por lo que se debe considerar entre los esquemas de tratamiento para este tipo de neoplasias
Subject(s)
Humans , Adult , Middle Aged , Male , Female , Drug Therapy , Lymphoma/therapy , Methotrexate/therapeutic useABSTRACT
En cuatro pacientes que presentaron granulocitopenia grave como resultado del uso de quimioterapia agresiva para el tratamiento de linfoma, se administró factor estimulante de colonias granulócito-macrófago (FEC-GM) a dosis de 10 ug/Kd/día. En todos los pacientes se observó una respuesta favorable con un incremento en el número de granulocitos en los primeros tres días de iniciado el tratamiento y alcanzándose valores normales al 5o. día. En ninguno de los casos se encontraron efectos tóxicos como resultado del FEC-GM. Estos resultados confirman la utilidad del FEC-GM en normalizar de manera rápida el número de granulocitos en pacientes que reciben regímenes de quimioterapia agresiva, disminuyendo asimismo el número y gravedad de las complicaciones