Prolonged Use of Zoledronic Acid (4 Years) Did Not Improve Outcome in Multiple Myeloma Patients.

BACKGROUND: Bisphosphonates, especially zoledronic acid (ZA), show antitumor effects in multiple myeloma (MM) and other neoplasms. The standard time for ZA administration has been 2 years. However, with improvement in overall survival (OS) in MM with new agents, it unclear whether ZA could be administered for a prolonged time to improve OS. PATIENTS AND METHODS: A total of 170 patients with untreated, symptomatic MM were randomly divided into a group to receive ZA for 4 years, with a control group to receive ZA for 2 years. All patients were treated with the same induction therapy and stem-cell transplantation. RESULTS: Actuarial curves at 5 years, showed that progression-free survival was 75% (95% confidence interval [CI], 64%-82%) and OS was 68% (95% CI, 60%-76%) in the 4-year group, which was not statistically significantly different compared with the control group: 72% (95% CI, 62%-78%) and 68% (95% CI, 60%-75%; P = .67). However, the 4-year group showed reduced skeletal events (21% occurrence rate); this was statistically significant compared with the control group: 43% (P < .001). CONCLUSION: Although ZA did not improve OS in patients with MM; it continued to be useful to reduce skeletal events, and thus improve better quality of life for patients.

Speckle-Tracking Echocardiography to Detect Cardiac Toxicity in Children Who Received Anthracyclines During Pregnancy.

Cardiac toxicities remain a possible risk to fetuses that received anthracyclines during pregnancy. The introduction of new echocardiographic techniques will improve the detection of early cardiac damage. Thus, we began a observational study using speckle-tracking echocardiography (STE) in children who had received anthracyclines during pregnancy, including the first trimester. From 2009 to 2013, we performed STE on patients > 5 years old, whose mothers had received anthracyclines during pregnancy. Siblings or cousins of equivalent age and gender were used as the control group. A total of 90 children fulfilled the entry criteria. Our results with STE were normal in all echocardiography parameters and did not show any differences when compared with the findings from the control group. We consider that the use of anthracyclines during pregnancy does not produce cardiac damage in newborns and can be safely administered, because no cardiac toxicity was evident in these children and it is of benefit to the mother.

Rituximab as consolidation therapy did not improve outcome in patients with diffuse large B-cell lymphoma at complete response after dose-dense chemotherapy (CHOP-14).

The authors started a clinical trial to assess the efficacy and toxicity of rituximab (R) as consolidation in patients with diffuse large B-cell lymphoma, with poor prognostic factors, who were in complete response (CR) after dose-dense chemotherapy (CHOP-14). Four hundred sixty-five untreated patients, with advanced stages (III and IV), older (median age >60 years old), and high clinical risk, were treated with dose-dense CHOP-14 (cyclophosphamide 1500 mg/m(2), i.v., day 1; vincristine 2 mg, i.v., standard dose, day 1; epirubicin 120 mg/m(2), i.v., day 1; and prednisone 60 mg/m(2), p.o., days 1-5) every 14 days for six cycles. If CR was achieved, the patients were allocated to receive R (375 mg/m(2), days 1, 8, 15, and 22) at 3 and 9 months after chemotherapy. Three hundred twenty-five patients achieved CR (70%) and were allocated to receive R (151 patients) or not (174 patients). Actuarial curves at 5 years showed that progression-free survival (PFS) was 51% (95% confidence interval [CI]: 44%-58%) in the R group and 53% (95% CI: 47%-59%) in the observation group (p=0.8). Overall survival (OS) was 65% (95% CI: 58%-71%) and 66% (95% CI: 59%-72%), respectively (p=0.78). Late toxicities were more frequent in the R group. The authors showed that the use of R as a consolidation treatment was not useful to improve PFS and OS and toxicity secondary to R was frequent. They did not recommend the use of R as consolidation in this patient setting.

Combined therapy in untreated patients improves outcome in nasal NK/T lymphoma: results of a clinical trial.

Nasal NK/T-cell lymphoma is a rare presentation of T-cell lymphoma in USA and in Europe, but is the most common presentation in Latin America. The lymphoma is associated with a worse prognosis even in the early stage. Until now, a better treatment has not been determined. We performed a prospective, open-label, controlled clinical trial to assess the efficacy and toxicity of the most common treatment options. We treated 427 patients, of whom 109 patients received radiotherapy (RT), 116 patients received chemotherapy (C), and 202 patients received combined therapy (CT), which were balanced according to stage and prognostic factors. Complete response was achieved in 91 % (95 % confidence interval CI 88-102 %) in CT arm 69 % (95 % CI 61-75 %) in RT arm; and 59 % (95 % CI 48-64 %) in C arm (p < 0.01). A progression-free disease was 91 % (95 % CI 83-96 %); 78 % (95 % CI 69-86 %); and 40 % (95 % CI 32-46 %), respectively (p < 0.01). Actuarial curves of overall survival at 5 years were as follows: 86 % (95 % CI 81-90 %), for CT; 64 % (95 % CI 59-70 %) for RT; and 45 % (95 % CI 39-51 %) for C (p < 0.001). Toxicity was mild and well tolerated. To our knowledge, this is the first controlled clinical trial, with a large number of patients and longer follow-up. Thus, we conclude that CT is the best therapeutic option in this setting of patients.

Rituximab in the treatment of diffuse large B-cell lymphoma primary of the lung.

Diffuse large B-cell lymphoma primary of lung (DLBCL-PL) is a rare presentation of extranodal lymphoma, in most cases chemotherapy-based anthracyclines: CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the treatment, with excellent outcome. The addition of rituximab to CHOP (R-CHOP) has been considered the gold standard in the treatment of nodal DLBCL. Thus, we assess in a large number of cases of DLBCL-PL whether the use of R-CHOP could improve survival in this setting of patients. Forty-two patients with DLBCL-PL, stage IE, age 65 years or younger, were treated with standard R-CHOP, no consolidation radiotherapy or maintenance therapy were considered. They were matched with patients who received CHOP alone to assess efficacy and toxicity. Complete response was observed in 35 patients (83%), and 7 patients were considered failure (16%). The study has a median follow-up of 42.8 months. Actuarial curves at 5 years showed that progression-free survival was 88 % and overall survival was 70 %. The results were not statistically different when compared retrospectively with patients who received CHOP alone. Treatment was well tolerated. The addition of rituximab to chemotherapy did not improve outcome in patients with DLBCL-PL.

Randomized clinical trial to assess the efficacy of radiotherapy in primary mediastinal large B-lymphoma.

PURPOSE: We developed a controlled clinical trial to assess the efficacy and toxicity of adjuvant-involved field radiotherapy (IFRT) in patients with primary mediastinal B-cell lymphoma that achieved complete response after the patients were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP-14). METHODS AND MATERIALS: Between January 2001 and June 2004, 124 consecutive patients who were in complete remission after dose dense chemotherapy and rituximab administration (R-CHOP14) were randomly assigned to received IFRT (30 Gy). Sixty-three patients received IFR, and 61 patients did not (control group). RESULTS: The study aimed to include 182 patients in each arm but was closed prematurely because in a security analysis (June 2004), progression and early relapse were more frequent in patients that did not received IFRT. Patients were followed until March 2009, at which point actuarial curves at 10 years showed that progression free-survival was 72% in patients who received IFR and 20% in the control group (p < 0.001), overall survival was 72% and 31%, respectively (p < 0.001). Acute toxicity was mild and well tolerated. DISCUSSION: Adjuvant radiotherapy to sites of bulky disease was the only difference to have an improvement in outcome in our patients; the use of rituximab during induction did not improve complete response rates and did affect overall survival; patients who received rituximab but not IFRT had a worse prognosis. CONCLUSIONS: The use of IFRT in patients with primary mediastinal B-cell lymphoma who achieved complete response remain as the best treatment available, even in patients that received rituximab during induction.

ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma.

BACKGROUND: Treatment for refractory lymphoma in frail patients (older, poor performance status, or concomitant diseases) has not been defined. PATIENTS AND METHODS: A total of 100 frail patients naive to rituximab therapy were allocated to be treated with ESHAP (etoposide, methylprednisolone, cytosine arabinoside, and platinum; 53 patients) or RESHAP (rituximab plus ESHAP; 47 patients). Granulocyte colony-stimulating factor was used to ameliorate the presence of severe granulocytopenia. RESULTS: Overall response rate (ORR) and complete response (CR) were similar among ESHAP and R-ESHAP (ORR, 33 patients [62%] and 28 patients [60%], respectively; CR, 20 patients [37%] and 18 patients [36%], respectively). Actuarial curves at 5 years showed that progression-free survival (PFS) and overall survival (OS) were similar: 51% and 31% in the ESHAP arm and 50% and 26%, respectively, in R-ESHAP. Toxicity was severe in both groups; grade 4 granulocytopenia was observed in 30% and 32% of ESHAP and R-ESHAP arms, respectively. Viral infections were more frequent in R-ESHAP (52 cases) than in ESHAP (3 cases). CONCLUSION: Frail patients, who generally have not been accepted in controlled clinical trials, can be treated with aggressive chemotherapy because tolerance is well and improvement in outcome is feasible. Although ESHAP retains the clinical efficacy previously reported in nonfrail patients, the addition of rituximab did not improve response rate, PFS, or OS.

Rituximab and dose-dense chemotherapy in primary testicular lymphoma.

BACKGROUND: Treatment of primary testicular lymphoma (PTL) remains unsatisfactory even in patients with good prognosis, as < 30% of patients are alive at 3 years. PATIENTS AND METHODS: We began a phase II study to assess efficacy and toxicity of a dose-dense cyclophosphamide/epirubicin/vincristine/prednisone (CEOP14) regimen with rituximab (CEOP14R) in 38 previously untreated patients with PTL with early-stage (I or II) and low-risk disease, followed by adjuvant radiation therapy and central nervous system prophylaxis. RESULTS: Complete response was 86% (similar to historical controls), but improvement in outcome was observed; with actuarial curves at 5 years, event-free survival was 70%, and overall survival was 66%. Toxicity was mild, and the regimen was well tolerated. CONCLUSION: The addition of rituximab to dose-dense chemotherapy improves outcome in this setting of patients who previously had been considered to have the poorest prognosis. It is important that these findings will be validated in multicentric, controlled clinical trials.

Rituximab and chemotherapy in primary gastric lymphoma.

PURPOSE: We performed a phase II clinical trial to assess the efficacy and toxicity of the addition of rituximab and conventional chemotherapy in primary gastric lymphoma (PGL). METHODS: Forty-two (42) patients with PGL, stage IE and IIE, and with low- or low-intermediate clinical risk were treated in a prospective longitudinal study with standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and rituximab (375 mg/m2, intravenously) on day 1 of each cycle administered every 21 days, for 6 cycles. The endpoint was to assess improvement in outcome measured by prolongation in event-free survival (EFS) and overall survival (OS). Complete response was achieved in 40 cases (95%) (95% confidence interval [CI]: 88%-102%). Relapse was observed in 2 cases. Two (2) patients died secondary to tumor progression. Thus, actuarial 5-year EFS was 95% (95 % CI: 87%-104%) and OS was 95% (95% CI: 88%-101%), which was not statistically different to historic controls. Acute toxicity was minimal and well tolerated, 4 cases developed late toxicity, 2 cases of herpes zoster infection, and 2 cases with granulocytopenia; in 1 case, the patient continued with mild granulocytopenia 3 years after treatment. CONCLUSIONS: The addition of rituximab to CHOP chemotherapy did not improve outcome in early-stage PGL.

Results of a phase III clinical trial: CHOP versus CMED in peripheral T-cell lymphoma unspecified.

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.

Interferon and low dose methotrexate improve outcome in refractory mycosis fungoides/Sézary syndrome.

Treatment of refractory mycosis fungoides and Sézary syndrome remain unsatisfactory. In this study, we assessed the efficacy and toxicity of low-dose methotrexate (10 mg/m(2), biweekly) and interferon (9.0 MU, three times a week) as induction therapy by 6 or 12 months, followed, if patients achieved a complete remission, by interferon maintenance until toxicity or relapse. In an intent-to-treat analysis, 158 patients were considered evaluable. Complete response (biopsy proven) was observed in 112 patients (49 [31%] at 6 months and 63 [49%] at 12 months); thus, the complete response rate was 74%. With a median follow-up of 155 months (range, 62-181), progression-free disease was 71% and overall survival was 69%. Acute toxicity was mild, treatment was well tolerated, and to date no late toxicity has been observed. We conclude that this regimen is a benefit to this setting of patients, with excellent outcome and mild toxicity.

Antitumor effect of zoledronic acid in previously untreated patients with multiple myeloma.

Bisphophonates are the treatment of choice to prevent skeletal events in patients with multiple myeloma. Some preclinical studies suggested that bisphophonates can be useful as antitumor drugs in some malignancies. We conducted a controlled clinical trial to assess if zoledronic acid can have this clinical activity. Ninety four patients with previously untreated multiple myeloma were treated with a conventional chemotherapy program: cyclophosphamide, vincristine, melphalan, and prednisone (CVMP) and were randomized to received either zoledronic acid (4 mg, iv, every 28 d) or not (control group). The end-point of the present study was to assess improvement in outcome, measured by event-free survival (EFS) and overall survival (OS), and the second-end point was to confirm the efficacy in preventing skeletal events. In an intent-to-treat analysis, all patients were available for efficacy and toxicity. Median follow up was 49.6 mo (range: 34-72 mo). Five year actuarial curves showed that EFS was 80% in the zoledronic acid group, which was statistically different from 52% in the control group (p < 0.01). Actuarial 5 yr OS was 80% in the zoledronic acid arm, and 46% in the control group (p < 0.01). Sketeletal events were more frequent in the control group when compared to zoledronic acid. Toxicity was mild. We confirm the efficacy of zoledronic acid to prevent skeletal events, but we felt that we can demonstrate that zoledronic acid has a clinical antitumor effect measured from a increase in complete response rate and EFS and OS that were better when compared with the control group. We began a controlled clinical trial with modern treatment (including transplant procedures) in combination with zoledronic acid to define the role of zoledonic acid in this setting of patients.

Dose dense (CEOP-14) vs dose dense and rituximab (CEOP-14 +R) in high-risk diffuse large cell lymphoma.

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.

Rituximab and escalated chemotherapy in elderly patients with aggressive diffuse large-cell lymphoma: a controlled clinical trial.

The treatment of elderly patients with aggressive malignant lymphoma has not been defined. The addition of rituximab to conventional chemotherapy has been reported to improve the outcome, but most patients have good prognostic factors (performance status < 2, no severe associated diseases, low or low-intermediate clinical risk). Thus, we developed a combined regimen, including escalated doses of anthracycline and rituximab. The endpoint was to improve event-free survival (EFS) and overall survival. Two hundred and four (204) patients were randomly assigned to receive an escalated chemotherapy regimen (CEOP) with escalated dose of epirubicin, compared to the same regimen and addition of rituximab. All patients had poor prognostic factors: high- or high-intermediate clinical risk, poor performance status, bulky disease, and more than 2 with extranodal involvement. In an intent-to-treat analysis, all patients were evaluable for efficacy and toxicity. The complete response rates were similar in both arms: 74% in chemotherapy and 78% in the rituximab + chemotherapy program. EFS and overall survival were similar: 77% and 84%, respectively, in combined chemotherapy and 75% and 81% in the rituximab-chemotherapy regimen. Toxicity was mild and well tolerated. In elderly patients with diffuse large-cell lymphoma and poor prognostic factors, rituximab did not improve their outcome.

Addition of a short course of chemotherapy did not improve outcome in patients with localized marginal B-cell lymphoma of the orbit.

OBJECTIVES: Primary orbital malignant lymphoma (POML) is a rare malignancy, thus treatment remains to be defined. The present study was designed to define if the use of radiotherapy is sufficient in these patients or if the use of adjuvant chemotherapy would improve the outcome. METHODS: Between 1983 and 1995, 98 previously untreated patients diagnosed with POML, stage IE, were randomly allocated to receive either radiotherapy (34-40 Gy) or the same radiotherapy combined with chemotherapy including anthracycline. The median follow-up was 11.4 years (range 9.8-10.8 years). RESULTS: Complete response was similar in both arms: 98% (95% confidence interval, CI: 89-100%) in the radiotherapy arm, and 100% (95% CI: 89-100%) in the combined therapy group. At a median follow-up of 16.4 years, event-free survival was 94% (95% CI: 87-100%) and 85% (95% CI: 88-100%), respectively. Overall survivals were: 96% (95% CI: 89-99%) and 91% (95% CI: 83-98%). No statistical differences were found. Acute and late toxicities were mild. CONCLUSIONS: The addition of chemotherapy is of no further benefit, since the results did not differ, thus, radiotherapy will be considered as the treatment of choice in POML patients.

Surgery and chemotherapy versus chemotherapy as treatment of high-grade MALT gastric lymphoma.

BACKGROUND AND OBJECTIVES: Treatment of high-grade MALT (mucosa-associated lymphoid tissue) gastric lymphoma remains uncertain. To assess efficacy and toxicity of the most common therapies--surgery followed by chemotherapy or chemotherapy alone--we began a controlled clinical trial in patients in early stage (I and II 1). METHODS: One hundred and two patients were randomized to be treated with surgery followed by six cycles of CEOP-Bleo (cyclophosphamide, epirubicin, vincristine, prednisone, and bleomycin at standard doses) (52 cases) or with chemotherapy alone (49 cases). RESULTS: Complete response rates were 94% [95% confidence interval (CI): 88-99%] and 96% (93-100%), respectively. Actuarial curves at 5 yr showed that event-free survival were 70% (95% CI: 59-74%) in patients treated with surgery and chemotherapy, that were not statistically significant to 67% (95% CI: 51-69%) in the patients who received chemotherapy (p = 0.5). Also, overall survival that was not statistically significant: 78% (95% CI: 70-88%) in the combined treatment and 76% (95% CI: 70-87%) in chemotherapy (p = 0.8). Acute and late toxicity were mild and well controlled. No acute leukemia or second neoplasm has been observed. CONCLUSIONS: The use of surgery and chemotherapy did not improve outcome in patients with early-stage high-grade gastric MALT lymphoma. It is apparent that chemotherapy alone is sufficient treatment in this select group of patients.

Residual disease after chemotherapy in aggressive malignant lymphoma: the role of radiotherapy.

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.

Novel therapy in multiple myeloma.

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.

Late cardiac toxicity secondary to treatment in Hodgkin's disease. A study comparing doxorubicin, epirubicin and mitoxantrone in combined therapy.

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.

Testicular lymphoma: organ-specific treatment did not improve outcome.

OBJECTIVES: To assess whether the use of an organ-specific treatment could improve event-free survival (EFS) and overall survival as endpoints in testicular lymphoma in the early stage: IE and IIE. METHODS: Thirty-four patients were selected to be treated with orchiectomy following six cycles of anthracycline-based combined chemotherapy and radiotherapy (scrotum and contralateral testis in stage IE, contralateral testis and lymph nodes in stage IIE). Prophylaxis to the central nervous system was administered with four monthly cycles of a high dose of methotrexate: 6 g/m2. RESULTS: Complete response was achieved in 33 cases (97%). However, relapses continue to be the rule; at a median follow-up of 74 months (range 61-120), 21 patients relapsed. Thus, actuarial curves at 5 years were 32% for EFS and 30% for overall survival, because all patients with failure and relapse died of tumor progression. Relapses were observed in uncommon sites: lung, bone marrow and as disseminate disease; no relapses were observed in irradiated sites of the central nervous system. CONCLUSIONS: Testicular lymphomas remain a problem as regards defining the optimal treatment. The use of a specific treatment based on organ-involved sites did not show any improvement in outcome. It is evident that more specific therapies need to be explored.