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E. Montserrat M.D,
J. García‐Conde,
N. Viñolas,
A. López‐Guillermo,
L. Hernández‐Nieto,
A. Zubizarreta,
J. Maldonado, A. Alcalá,
M.‐V. Faura,
A. Llorente,
J. Bladé,
M. Fontanillas
[show abstract]
[hide abstract]
ABSTRACT: From May 1985 to May 1989, 175 patients with previously untreated aggressive non-Hodgkin's lymphoma were randomized to receive CHOP or ProMACE-CytaBOM. Eligibility criteria included follicular large-cell, diffuse small cleaved-cell, diffuse mixed, diffuse large-cell and immunoblastic lymphoma with an Ann Arbor stage II, III or IV. One hundred and forty-eight patients were evaluable. There were no significant differences between the 2 treatments in response rate (83.5% [57.5% CR] for CHOP vs. 88% [62% CR] for ProMACE-CytaBOM), time to treatment failure (29% vs. 31% at 5 yr), or overall survival (42% in both groups at 5 yr). Furthermore, there were no significant differences between the 2 regimens when response rates and outcome were analyzed for different prognostic subgroups. Toxicity was not significantly different between the 2 regimens, although only 1 patient died as result of treatment-related toxicity in the CHOP arm compared to 6 patients in the ProMACE-CytaBOM group (p = 0.126). In conclusion, in this study ProMACE-CytaBOM has not proved to be superior to CHOP in aggressive lymphomas. This trial gives support to the notion that CHOP still is the standard chemotherapy for aggressive lymphomas, and that new treatment approaches for these lymphomas should be compared to CHOP.
European Journal Of Haematology 04/2009; 57(5):377 - 383. · 2.61 Impact Factor
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J J Ortega,
J M Ribera,
A Oriol,
P Bastida,
M E González,
C Calvo,
I Egurbide,
J M Hernández Rivas,
C Rivas, A Alcalá,
J Besalduch,
J Maciá,
S Gardella,
M Carnero,
J M Lite,
F Casanova,
M Martinez,
M Fontanillas,
E Feliu,
J F San Miguel
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the impact of early and delayed consolidation chemotherapy on the outcome of children with acute lymphoblastic leukemia (ALL) stratified according to risk groups.
From 1989 to 1994, 195 children (< or = 15 years old) diagnosed as having ALL (ALL-L3 excluded) in 15 Spanish hospitals entered the prospective, randomized PETHEMA ALL-89 trial. Patients were stratified into low-risk (LR), intermediate-risk (IR) and high-risk (HR) groups according to their initial features and the rate of response to induction therapy. LR-ALL patients were randomized to receive or not early consolidation chemotherapy (C-1). After receiving C-1, IR patients were randomized to receive or not delayed consolidation chemotherapy (C-2). HR patients received C-1 and C-2 chemotherapy. Standard maintenance chemotherapy was administered to all patients for 2 years. High doses of intravenous methotrexate and 12 triple intrathecal doses were given as prophylaxis against central nervous system (CNS) disease.
The mean (and standard deviation) age was 6 (4) years and 120 patients were males. Fourteen patients had early pre-B-ALL, 149 common or pre-B-ALL, and 32 T-ALL. Complete remission (CR) was attained in 189 patients (97%), 11 of whom (6%) had a slow response. Risk group stratification after CR was: LR 89, IR 50 and HR 56 patients (including a subset of 26 patients at very high risk). Ten-year event-free survival (EFS) and overall survival (OS) probabilities for the whole series were 58% (95% CI: 52-64%) and 69% (61-77), respectively, with a median follow-up of 8.7 years. Dividing the patients according to risk group, the 10-year EFS and OS probabilities in the LR group were 71% (63-79) and 86% (80-92), respectively; in the IR group 69% (57-81) and 76% (64-88), respectively, and in the HR group 30% (18-42) and 44% (32-57), respectively. For LR patients receiving C-1, EFS and OS were 79% (57-92) and 90% (82-98), respectively, versus 62% (48-76) and 66% (51-81) in patients not receiving C-1 (p= 0.06). For IR patients, EFS and OS were significantly improved in those receiving early and delayed consolidation (EFS 87% (74-88) vs. 52% (41-70), and OS 92% (87-97) vs. 61% (51-71)(p=0.036). Prognostic factors for EFS identified in multivariable analyses were: age >10 years in the LR group (OR 3.5, 95% CI 1.3-9.5, p=0.01), and treatment with C-2 in IR patients (OR 5.0, 95% CI 1.4-17.8, p=0.01). The CNS relapse rate was 4% for all the series (including the HR subset). Tolerance to treatment was good.
In this study, early consolidation seemed to improve the prognosis of children with LR-ALL, but differences in EFS were not significant. Delayed consolidation had a favorable influence on the outcome of IR-ALL. CNS preventive treatment without cranial irradiation was effective in all the groups of ALL patients.
Haematologica 06/2001; 86(6):586-95. · 6.42 Impact Factor
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J Bladé,
J F San Miguel,
M Fontanillas,
J Esteve,
J Maldonado, A Alcalá,
S Brunet,
J García-Conde,
J Besalduch,
M J Moro, [......],
J M Martí,
J Hernández-Martín,
F Ortega,
C Besses,
J M Ribera,
J Trujillo,
M L Escudero,
C Rozman,
J Estapé,
E Montserrat
[show abstract]
[hide abstract]
ABSTRACT: Melphalan and prednisone (MP) has been the standard treatment for multiple myeloma (MM) for the last 30 years. Combination chemotherapy at conventional doses has not shown a significant prolongation of survival when compared to MP. There are few data comparing conventional chemotherapy at standard doses with conventional treatment at higher doses. We present the long-term outcome of 914 patients from two randomized trials comparing three different dose intensity regimens.
From 1 January, 1985 to 31 December, 1989, 487 patients were randomized between MP (melphalan 9 mg/m(2) p.o. and prednisone 60 mg/m(2) days 1-4) and alternating VCMP (vincristine 1 mg i.v. on day 1, cyclophosphamide 500 mg/m(2) i.v. on day 1, melphalan 6 mg/m(2) p.o. on days 1-4, and prednisone 60 mg/m(2) on days 1-4) and VBAP (vincristine 1 mg i.v. on day 1, BCNU and doxorubicin 30 mg/m(2) i.v. each on day 1, and prednisone 60 mg/m(2) on days 1-4). From 1 January, 1990 to 31 May, 1994, 427 patients were randomized between VCMP/VBAP at the above detailed doses (VCMP/VBAP 'SD') and the same regimen increasing the doses of cyclophosphamide and doxorubicin from 500 to 1200 mg/m(2) and from 30 to 50 mg/m(2), respectively (VCMP/VBAP 'HD').
Increasing dose intensity produced a significantly higher partial response rate (31% vs 45% vs 51% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P < 0.01). However, a significantly early death rate was observed in the HD arm (7.7, 7.5 and 12.1% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = 0.05). Median duration of response (20 vs 18 vs 19 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) and median survival (25 vs 31 vs 29 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) were similar in the three groups. MP produced a higher degree of thrombocytopenia than combination chemotherapy at standard (P = 0.002) or high dose (P = 0.01), this leading to a significantly higher dose reduction in the MP arm (P < 0.001 and P = 0.003 for VCMP/VBAP 'SD' and VCMP/VBAP 'HD', respectively).
In these trials the response rate significantly correlated with the regimen intensity. However, no significant differences in response duration and survival were found. This highlights the limited role of conventional chemotherapy in MM and the need for further trials, aimed at determining the impact of new treatment approaches such as high-dose therapy/autotransplantation.
The Hematology Journal 01/2001; 2(4):272-8. · 1.86 Impact Factor
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A López-Guillermo,
J García-Conde,
A M Alvarez-Carmona,
P León,
J Maldonado, A Alcalá,
A Zubizarreta,
R Sancho-Tello,
F Carbonell,
E Contreras,
C Besses,
A Hernando,
M Fontanillas,
E Montserrat
[show abstract]
[hide abstract]
ABSTRACT: To compare standard chemotherapy CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) with the regimen CHOP/VIA (VP-16, iphosphamide and cytarabine) in terms of response to therapy, response duration, survival and toxicity in patients with aggressive lymphoma.
132 patients (84 males and 48 females; median age, 55 years) were included from 12 Spanish Institutions, diagnosed of non-Hodgkin's lymphoma of intermediate or high grade, in stages II-IV and previously untreated. Patients were randomized to receive CHOP or CHOP/VIA.
After excluding 14 not assessable cases, 62 patients (52.5%) received CHOP, and 56 (47.5%) CHOP/VIA. No significant differences were found on main prognostic factors between such groups. Response was assessable in 114 cases (CHOP: 61; CHOP/VIA: 53) 39 patients (64%) receiving CHOP achieved complete response (CR), and 2 (3%) partial response (PR), whereas in the CHOP/VIA group CR and PR rates were 63% (34/53), and 7% (4/53), respectively. 14 patients (36%) treated with CHOP and 12 (35%) treated with CHOP/VIA eventually relapsed, with an actuarial risk of relapse at 36 months of 43% and 40%, respectively. Median survival was 37 months. No differences were found between both therapeutic groups, with an overall survival at 36 months from diagnosis of 53.5% (CI 95%: 40-67) for CHOP and 48% (CI 95%: 34-62) for CHOP/VIA. Finally, toxicity was not different for both arms.
In the present study in patients with aggressive NHL chemotherapy regimens CHOP and CHOP/VIA showed similar results in terms of response, response duration, survival and toxicity.
Medicina Clínica 06/1998; 110(16):601-4. · 1.38 Impact Factor
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E Montserrat,
J García-Conde,
N Viñolas,
A López-Guillermo,
L Hernández-Nieto,
A Zubizarreta,
J Maldonado, A Alcalá,
M V Faura,
A Llorente,
J Bladé,
M Fontanillas,
J Estapé
[show abstract]
[hide abstract]
ABSTRACT: From May 1985 to May 1989, 175 patients with previously untreated aggressive non-Hodgkin's lymphoma were randomized to receive CHOP or ProMACE-CytaBOM. Eligibility criteria included follicular large-cell diffuse small cleaved-cell, diffuse mixed, diffuse large-cell and immunoblastic lymphoma with an Ann Arbor stage II, III or IV. One hundred and forty-eight patients were evaluable. There were no significant differences between the 2 treatments in response rate (83.5% [57.5% CR] for CHOP vs. 88% [62% CR] for ProMACE-CytaBOM), time to treatment failure (29% vs. 31% at 5 yr), or overall survival (42% in both groups at 5 yr). Furthermore, there were no significant differences between the 2 regimens when response rates and outcome were analyzed for different prognostic subgroups. Toxicity was not significantly different between the 2 regimens, although only 1 patient died as result of treatment-related toxicity in the CHOP arm compared to 6 patient in the ProMACE-CytaBOM group (p = 0.126). In conclusion, in this study ProMACE-CytaBOM has not proved to be superior to CHOP in aggressive lymphomas. This trial gives support to the notion that CHOP still is the standard chemotherapy for aggressive lymphomas, and that new treatment approaches for these lymphomas should be compared to CHOP.
European Journal Of Haematology 12/1996; 57(5):377-83. · 2.61 Impact Factor
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J Bladé,
M Muñoz,
M Fontanillas,
J San Miguel, A Alcalá,
J Maldonado,
C Besses,
M J Moro,
J García-Conde,
C Rozman,
E Montserrat,
J Estapé
[show abstract]
[hide abstract]
ABSTRACT: The purposes of the present study have been to analyse the presenting features, response to therapy and survival of myeloma patients aged 70 years or more, in comparison to younger patients. From January 1985 to December 1989, 487 patients with multiple myeloma (MM) were randomized to receive melphalan and prednisone (MP) versus alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, BCNU, adriamycin, and prednisone (VBAP). The subset of 178 patients who were 70 or more years is the subject of this study, whereas the 309 patients younger than 70 years were used as a control group. The presenting features and response to chemotherapy of older patients were no different to those of the younger population. However, the survival of elderly patients was significantly shorter (median 23.4 vs. 33.5 months, p < 0.001). The overall response rate to MP in older patients was 50% (28% objective plus 22% partial response) compared with 61% (44% objective plus 17% partial response) to combination chemotherapy (p = not significant). Myelosuppression was moderate in both arms, although MP produced a higher degree of thrombocytopenia. There were no significant differences in survival between patients given MP versus VCMP/ VBAP (median, 20 vs. 27 months, p = 0.2). Response to treatment was associated with a significantly longer survival. Older patients with symptomatic myeloma tolerate chemotherapy and should be offered treatment.
Age and Ageing 09/1996; 25(5):357-61. · 3.09 Impact Factor
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J Bladé,
J F San Miguel,
M Fontanillas, A Alcalá,
J Maldonado,
J García-Conde,
E Conde,
G Conzález-Brito,
M J Moro,
M L Escudero,
J Trujillo,
A Pascual,
C Rozman,
J Estapé,
E Montserrat
[show abstract]
[hide abstract]
ABSTRACT: To analyze the outcome of patients with multiple myeloma (MM) who were potential candidates for early high-dose therapy (HDT) intensification followed by autotransplantation from a series treated with conventional chemotherapy.
From January 1985 through December 1989, 487 patients with symptomatic MM were entered onto a randomized study to compare melphalan and prednisone (MP) versus vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) /vincristine, carmustine (BCNU), doxorubicin, and prednisone (VBAP). The sub-group of 77 patients who could have been candidates for early intensification with HDT followed by stem-cell support (ie, < 65 years of age, stage II or III disease, performance status < 3, and objective or partial response to initial chemotherapy) are the subjects of this report.
Seventy-seven of 487 patients could have been candidates for early intensification. The median age was 56 years (range, 27 to 64). At diagnosis, 12% had abnormal renal function, 16% hypercalcemia, and 42% serum beta 2-microglobulin level > or = 6 mg/L; 62% had stage III disease at diagnosis. Thirty-six patients were initially treated with MP and 41 with VCMP/VBAP. The median response duration to initial chemotherapy was 22 months, and the actuarial probability of being in continued first response at 5 years was 14%. After a median follow-up time of 58 months, 59 patients have died, one was lost to follow-up evaluation, and 17 are still alive 69 to 119 months after initial chemotherapy. The median survival time from initiation of treatment was 60 months and from the time when autotransplantation would be considered, 52 months. The only independent prognostic parameter for survival was renal function at diagnosis.
The median survival time of patients with MM who are less than 65 years of age and who respond to initial chemotherapy is 5 years. This survival duration is similar to that reported in selected series of patients given early HDT and stresses the importance of ongoing randomized trials to determine the role of HDT in the treatment of younger myeloma patients.
Journal of Clinical Oncology 07/1996; 14(7):2167-73. · 18.37 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: To determine whether combination chemotherapy with alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, carmustine (BCNU), Adriamycin (doxorubicin; Farmitalia, Carlo-Erba Laboratories, Spain), and prednisone (VBAP) is better than the standard melphalan-prednisone (MP) regimen in multiple myeloma (MM).
From January 1985 to December 1989, 28 institutions of the Spanish Cooperative Group for Hematological Malignancies Treatment, Spanish Society of Hematology (PETHEMA) entered 487 eligible patients with symptomatic MM into the study. Patients were randomized to receive either MP or alternating courses of VCMP and VBAP. Logistic regression and the Cox proportional hazards models were used to assess the association between patients' characteristics and response rate and survival, respectively.
Among 449 patients who were assessable for response, the overall response rate to MP was 51.8% (31.5% objective response plus 20.3% partial response) as compared with 62.7% (45.2% objective response plus 17.5% partial response) to VCMP/VBAP (P = .025). Also, a significantly higher proportion of objective responses was observed with combination chemotherapy (45.2% v 31.5%; P = .004). The factors associated with an unfavorable response rate in the overall series were low platelet count, treatment with MP, high creatinine level and immunoglobulin, (IgG) monoclonal (M)-component. No significant differences were found when survival rates of both groups of patients were compared. However, patients with IgA myeloma treated with VCMP/VBAP survived significantly longer than those who received MP (median, 20.2 v 38.4 months; P < .005).
These results indicate that combination chemotherapy improves response rate in MM. However, this does not result in a significantly different survival rate, except for patients with IgA myeloma, who survive significantly longer with combination chemotherapy.
Journal of Clinical Oncology 06/1993; 11(6):1165-71. · 18.37 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: A total of 65 patients (35 male/30 female) with multiple myeloma primarily (33) or secondarily (32) resistant to melphalan and prednisone were treated with vincristine, carmustine (BCNU), doxorubicin, and high-dose dexamethasone (VBAD) at 4-week intervals. Among 60 evaluable patients the overall response was 36.6% (21.6% objective response plus 15% improvements). The response rate was significantly higher in primarily resistant patients than in those becoming resistant after a prior response (48.4 vs. 24.1%, P < 0.05). The median duration of response was 17.5 months. When survival of responders and non-responders were compared by the conventional method, a highly significant difference was observed (P < 0.001). However, using the Mantel and Byar procedure and the landmark method, only a trend for longer survival in the responders was registered. These results indicate that although VBAD is effective in at least one third of patients with advanced multiple myeloma resistant to melphalan, its impact on survival is limited.
European Journal of Cancer 01/1992; 29A(1):57-60. · 5.54 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: We have analyzed 117 younger patients with chronic lymphocytic leukemia (CLL) (mean age, 44.5 years; SD, 4.8; range, 19 to 49; male/female ratio, 2.08) with three main objectives: (1) to see whether these patients have distinctive presenting clinical features; (2) to investigate the impact of the disease on survival; and (3) to analyze whether already well-known prognostic factors are also useful when applied to these patients. As compared with an older age population (greater than or equal to 50 years), there were no major differences in presenting features except for an increased proportion of males (2.08 v 1.21; P less than .025) and a higher hemoglobin level (13.47 +/- 2.70 g/dL v 12.84 +/- 2.77 g/dL; P less than .05) in the younger group. Median survival is 12.3 years (expected median from a control group, 31.2 years). Clinical stages, bone marrow patterns, blood lymphocyte counts, and its doubling time are all useful to separate different risk groups of patients. Whereas patients with favorable prognostic factors have a survival probability of about 80% 14 years after diagnosis, those with poor prognostic features have a median survival of less than 3 years. It is concluded that CLL in younger adults has no major distinctive presenting features and that known prognostic factors are useful to separate different risk groups of patients. These results should be of help in planning therapy for younger persons with CLL.
Blood 10/1991; 78(6):1545-51. · 9.90 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Between January 1985 and December 1988, 386 patients with multiple myeloma were randomized to receive either MP or combination chemotherapy based on alternating cycles of VCMP and VBAP. The major prognostic parameters did not differ significantly between both treatment groups. A significantly higher proportion of objective responses was observed with combination chemotherapy as compared to MP (47.8 vs 32.2, P = 0.01). The median survival for all patients was 33.5 months. So far no significant differences were found when comparing the survival curves from both groups of patients. However, the median survival of MP-treated patients is 26.8 months, whereas the median survival of patients receiving VCMP/VBAP has not yet been reached. The definitive analysis must await the evaluation of all patients entered into the study and a longer follow-up time.
Blut 07/1990; 60(6):319-22.
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J. Bladé,
J. San Miguel, A. Alcalá,
J. Maldonado,
J. García-Conde,
M. J. Moro,
M. A. Sanz Sanz,
C. Alonso,
A. Zubizarreta,
C. Besses, [......],
J. R. Mayans,
J. Sanchis,
R. Jimenez Galindo,
J. Tortosa,
F. Ortega,
A. Domingo,
M. V. Faura,
M. Daniels,
C. Rozman,
J. Estapé
[show abstract]
[hide abstract]
ABSTRACT: Between January 1985 and December 1988, 386 patients with multiple myeloma were randomized to receive either MP or combination chemotherapy based on alternating cycles of VCMP and VBAP. The major prognostic parameters did not differ significantly between both treatment groups. A significantly higher proportion of objective responses was observed with combination chemotherapy as compared to MP (47.8 vs 32.2,P = 0.01). The median survival for all patients was 33.5 months. So far no significant differences were found when comparing the survival curves from both groups of patients. However, the median survival of MP-treated patients is 26.8 months, whereas the median survival of patients receiving VCMP/VBAP has not yet been reached. The definitive analysis must await the evaluation of all patients entered into the study and a longer follow-up time.
Annals of Hematology 05/1990; 60(6):319-322. · 2.62 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Ninety-six previously untreated patients (67 males/29 females; mean age: 63 years; range: 46-84) with CLL in stage B (62 cases) or C (34 cases) were randomized to be treated with either chlorambucil (0.4 mg/kg orally days 5 and 6) plus prednisone (60 mg/m2 orally days 1 to 4) (CL + PDN) every 2 weeks or cyclophosphamide (160 mg/m2 orally days 1 to 4), melphalan (6 mg/m2 orally days 1 to 4), and prednisone (60 mg/m2 orally days 1 to 4) (CMP) every 3 weeks for 10 months. Forty-eight patients were treated with CLR + PDN, and the remaining 48 with CMP. The following types of response were considered: complete response (CR): total disappearance of symptoms and signs related to the disease. Partial response (PR): shift of the disease to a less advanced stage. Stable disease (SD) no change in the stage after treatment. Progressive disease (PD): progression of the disease to a more advanced stage. Thirty-six (75%) responses (27% CR) with CLR + PDN and 26 (54.5%, 12.5% CR) with CMP were observed (p = 0.054). Although more responses were achieved in stage B (69%, 24% CR) than in stage C (54%, 12% CR) this difference did not achieve statistical significance. Survival was statistically not different for those patients treated with LCR + PDN as compared to those receiving CMP.(ABSTRACT TRUNCATED AT 250 WORDS)
Nouvelle revue française d'hématologie 02/1988; 30(5-6):429-32.
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[show abstract]
[hide abstract]
ABSTRACT: Ninety-six patients with advanced chronic lymphocytic leukemia (CLL) (Stage C; anemia and/or thrombocytopenia of nonimmune origin) were randomized to receive either chlorambucil (CLR) (0.4 mg/kg orally, day 6) plus prednisone (PDN) (60 mg/m2 orally, days 1-5) every 2 weeks or cyclophosphamide (600 mg/m2 intravenously, day 6), vincristine (1 mg/m2 intravenously, day 6) and prednisone (60 mg/m2 orally, days 1-5) (COP) each month for 5 months. Complete remission (CR) was defined as the total disappearance of signs and symptoms related to the disease. Partial remission (PR) was considered to be achieved when, after treatment, the clinical stage changed to a less advanced one. Thirty (59%) responses (8% CR) with CLR plus PDN and 14 (31%, 2% CR) with COP were observed (P less than 0.01). The survival was not significantly different for the two groups. Patients previously treated had a lower number of responses (11/35, 31%) than those with no previous treatment (33/61, 54%) (P less than 0.05). Patients who attained a CR or a good PR had longer survivals (median not reached) than those with a poor PR (median, 25.2 months) or those who did not respond to treatment (median, 11.5 months) (P less than 0.005).
Cancer 12/1985; 56(10):2369-75. · 4.77 Impact Factor
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Bibliotheca haematologica 02/1984;
