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PubMed1994

A randomized study in stage IIIB and IV Hodgkin's disease comparing eight courses of MOPP versus an alteration of MOPP with ABVD: a European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group and Groupe Pierre-et-Marie-Curie controlled clinical trial.

PURPOSE: We report a prospective randomized study comparing the relative efficacy of alternating chemotherapy mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) with the standard MOPP chemotherapy in patients with stage IIIB and IV Hodgkin's disease (HD). The purpose is to study the influence of time of remission on clinical outcome. PATIENTS AND METHODS: After two courses of MOPP, patients were randomized to receive six further courses of MOPP, or two courses of ABVD followed by two courses of MOPP and two courses of ABVD. Radiotherapy was given to areas presenting with masses > or = 5 cm and to residual masses after course no. 4. Evaluation of response (complete remission [CR]) took place after two courses (CR2), after four courses (CR4), at the end of chemotherapy (CR8), and after additional radiotherapy (CR(CT + RT)). Logistic regression analysis was used to study prognostic factors for response at the end of chemotherapy. Cox analysis was used to study prognostic factors for survival. Two hundred seven patients were registered, 192 (93%) of whom were randomized. RESULTS: The CR rate at the end of chemotherapy (CR8) was similar in both arms (57% v 59%). However, there were more progressions in the MOPP arm compared with the MOPP/ABVD arm (23% v 8%, P = .014). A significantly higher failure-free survival (FFS) rate was found in the MOPP/ABVD arm (60% v 43% at 6 years, P = .025). There was no difference in the relapse-free survival (RFS) or survival rate. Of patients not in CR4, only 28% still reached a CR8. RFS at 6 years of patients with CR4 (69%) was not different from that of patients with CR8 (68%); patients with a CR(CT + RT)) had a lower RFS rate (48%). CR4 (P < .001) predicted strongly for final remission at the end of chemotherapy. Cox analysis showed that age more than 50 years, six or more involved lymph node areas, no CR by the fourth cycle, chemotherapy with MOPP alone, and no radiotherapy were unfavorable factors for survival. CONCLUSION: MOPP/ABVD chemotherapy significantly improved response and FFS rates, but had no influence on RFS and survival rates. Early CR (CR4) is an important factor for final remission and might be used to select a group of patients with a good prognosis.

Adolescent↗
PubMed1995

Gonadal function following chemotherapy for Hodgkin's disease: a comparative study of MVPP and a seven-drug hybrid regimen.

PURPOSE AND METHODS: Gonadal function was assessed in 89 patients after chemotherapy for Hodgkin's disease (HD). Thirty-seven patients had received mechlorethamine, vinblastine, prednisolone, and procarbazine (MVPP) and 52 patients, a hybrid combination of chlorambucil, vinblastine, prednisolone, procarbazine, doxorubicin, vincristine, and etoposide (ChIVPP/EVA). Fifty men (MVPP, n = 21; ChIVPP/EVA, n = 29) with a median age of 26 years (range, 16 to 54) and 39 women (MVPP, n = 16; ChIVPP/EVA, n = 23) with a median age of 30 years (range, 15 to 47) were studied at a median of 30 months (range, 4 to 83) following chemotherapy. RESULTS: Semen analysis showed azoospermia in 35 of 37 men, and increased serum follicle-stimulating hormone (FSH) levels in this group confirmed severe germinal epithelial damage. Analysis of pretreatment semen in 28 men showed azoospermia in one, oligospermia in four (sperm count < 20 x 10(6)/mL), and a normal sperm count in the remaining 23. In the women, 26 of 34 (76%) with a regular menstrual cycle before commencing chemotherapy became amenorrheic following treatment. Menses returned in 10 women, who had a median age of 25 years (range, 21 to 34), and there were two pregnancies in this group. In the other 16, with a median age of 36 years (range, 27 to 47), amenorrhea persisted and premature ovarian failure was confirmed by increased serum gonadotrophins and reduced estradiol (E2) concentrations. Of the original eight women in whom menses were maintained following treatment, two subsequently developed amenorrhea and the clinical and biochemical features of an early menopause. In total, 18 of 34 women (53%) required hormone replacement therapy for chemotherapy-induced ovarian failure. CONCLUSION: There was no statistically significant difference in the frequency or severity of gonadal dysfunction between MVPP- and ChIVPP/EVA-treated patients. We conclude that both of these chemotherapy schedules cause substantial damage to gonadal function in both sexes.

Adolescent↗
PubMed1995

Efficacy of four different regimens in 64 mantle-cell lymphoma cases: clinicopathologic comparison with 498 other non-Hodgkin's lymphoma subtypes. European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group.

PURPOSE: Before recognizing mantle-cell lymphoma (MCL) as a distinct entity, these patients were grouped into low-grade (LG) or intermediate-/high-grade categories (IGHG) according to the Working Formulation and received various therapies. This was a unique opportunity to evaluate characteristics, behavior, response to treatment, and outcome of patients with MCL from two phase III trials conducted by the European Organization for the Research and Treatment of Cancer (EORTC): EORTC 20855 IGHG and EORTC 20856 LG. PATIENTS AND METHODS: After histologic review, 64 diagnosed MCL patients (29 IGHG and 35 LG) were compared with other patients in their respective trials. In the IGHG group, patients received cyclophosphamide, doxorubicin, teniposide (VM26), prednisone, vincristine, and bleomycin (CHVmP-VB) or modified doxorubicin, cyclophosphamide, etoposide (VP 16), mechlorethamine, vincristine, procarbazine, and prednisone (ProMACE-MOPP). In the LG group, after receiving cyclophosphamide, vincristine, and prednisone (CVP) induction, patients were randomized between maintenance treatment with interferon alfa-2a (IFN) or no further treatment. RESULTS: MCL patients compared with IGHG subtypes showed a similar overall survival and response rate, but shorter duration of response and progression-free survival. Comparing with LG patients, their response rate, duration of response, and progression-free survival showed no difference, while their overall survival was nearly twice shorter. MCL patients treated with CHVmP-VB had the longest survival. No treatment showed any significant improvement in terms of progression-free survival. CONCLUSION: These data confirm that MCL represents a clinicopathologic entity. In terms of survival, it behaves like IGHG subtypes, while in terms of progression-free survival, it behaves like LG lymphoma. It is still not clear which first-line treatment offers patients with MCL the best chance to obtain both a complete response (CR) and a long-term survival.

Adolescent↗
PubMed1995

Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage Hodgkin's disease: a preliminary report.

PURPOSE: Although survival rates have improved for patients with bulky and advanced-stage Hodgkin's disease (HD), current treatments entail substantial acute morbidity and risks for late effects such as infertility, second malignancies, and cardiopulmonary toxicities. A novel, brief chemotherapy regimen (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone [Stanford V]) was designed to shorten the duration of treatment, significantly reduce cumulative doses of alkylating agents, doxorubicin, and bleomycin, and maintain dose-intensity (DI). This brief chemotherapy was combined with radiation therapy (RT) to bulky disease sites. METHODS: Since May 1989, 65 previously untreated patients were treated for stage II HD with bulky mediastinal involvement (n = 21) or for stage III or IV HD (n = 44). Patients received weekly chemotherapy for 12 weeks. Consolidative RT was given to the first 25 patients to sites of initial bulky disease or radiographic abnormalities that persisted after chemotherapy; in the remaining 40 patients, RT was limited to bulky disease (adenopathy > or = 5 cm and/or macroscopic splenic nodules defined by computed tomography [CT]). RESULTS: With a median follow-up period of 2 years, actuarial 3-year survival rate is 96% and failure-free survival (FFS) rate is 87%. The 3-year FFS rate is 100% for stage II patients with bulky mediastinal disease and 82% for patients with stage III to IV disease. There were no treatment-related deaths. In a preliminary analysis on a subset of patients, female and male fertility appears to be preserved. CONCLUSION: These preliminary results indicate that the Stanford V chemotherapy regimen with or without RT is well-tolerated and effective therapy for bulky, limited-stage, and advanced-stage HD. Less cumulative exposure to alkylating agents, doxorubicin, and bleomycin and limited use of radiation is expected to decrease risks for second neoplasms and late cardiopulmonary toxicity. Based on these results, the Stanford V chemotherapy with or without RT regimen deserves further study in the context of a randomized clinical trial.

Actuarial Analysis↗
PubMed1995

Etoposide, vinblastine, and doxorubicin: an active regimen for the treatment of Hodgkin's disease in relapse following MOPP. Cancer and Leukemia Group B.

PURPOSE: To evaluate the activity and toxicity of combined etoposide, vinblastine, and doxorubicin (EVA) in advanced Hodgkin's disease (HD) in relapse from or refractory to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). PATIENTS AND METHODS: Eligible patients were more than 15 years of age and had received only one prior course of MOPP and were in relapse with measurable disease. The EVA regimen (etoposide 100 mg/m2 intravenously [IV] on days 1, 2, and 3; vinblastine 6 mg/m2 IV on day 1; and doxorubicin 50 mg/m2 IV on day 1) was administered every 28 days for a minimum of four and a maximum of six cycles. Patients were restaged at 3 and 6 months. RESULTS: Forty-five eligible patients were treated, with an overall response rate of 73%. There were 40% complete responses (CRs) and 33% partial responses (PRs). The median follow-up time in 42 months. The median time to treatment failure (TTF) is 10 months, with 31% continuing progression-free. Eighteen patients achieved a second CR, with only seven recurrences in that group. Failure-free survival and overall survival were significantly better in patients whose first MOPP-induced remission was longer than 12 months and who were free of B symptoms at relapse. Toxicity was primarily myelosuppression, which resulted in two toxic deaths. Pulmonary toxicity was not observed. CONCLUSION: EVA is an effective second-line regimen for the treatment of HD in relapse following MOPP chemotherapy.

Adolescent↗
PubMed1995

Results of a randomized trial comparing MVPP chemotherapy with a hybrid regimen, ChlVPP/EVA, in the initial treatment of Hodgkin's disease.

PURPOSE AND METHODS: Between December 1984 and August 1992, 423 patients with newly diagnosed Hodgkin's disease (HD) were entered onto a randomized clinical trial that compared the regimen of mechlorethamine, vinblastine, procarbazine, and prednisone (MVPP) with a doxorubicin-containing hybrid regimen (chlorambucil, vinblastine, procarbazine, and prednisone/etoposide, vincristine, and doxorubicin [ChlVPP/EVA]). Median age for the group was 29.5 years (range, 15.2 to 68.8), and 52% had bulk disease. RESULTS: After chemotherapy, patients in the hybrid arm of the trial had a higher complete remission (CR) rate (68.1% v 55.3%) and a lower failure rate (2.4% v 12.5%) than those in the MVPP arm. There were also fewer deaths during treatment in the hybrid arm of the trial (five v 13). With a median follow-up period for survivors of 4.5 years (range, 0 to 9), actuarial 5-year progression-free survival (PFS) for all cases is 80% in the hybrid arm and 66% in the MVPP arm (P = .005). A nonsignificant trend toward a better overall survival in the hybrid arm of the trial has also been identified. CONCLUSION: These results suggest that ChlVPP/EVA hybrid is superior to MVPP in the treatment of HD. It has therefore been adopted as standard first-line therapy at the two centers.

Adolescent↗
PubMed1996

Alternating versus hybrid MOPP and ABVD combinations in advanced Hodgkin's disease: ten-year results.

PURPOSE: To compare, in a prospective randomized trial, the efficacy of two different sequences of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy in untreated advanced Hodgkin's disease. PATIENTS AND METHODS: From June 1982 to September 1990, 427 consecutive previously untreated patients with pathologic stage IB, IIA bulky, IIB, III (A and B), and IV (A and B) disease were prospectively randomized to receive two different sequences of MOPP and ABVD for a minimum of six cycles followed by radiotherapy (median dose, 30 Gy) to the nodal site(s) of pretreatment bulky disease. Of 415 assessable patients, 211 received one cycle of MOPP monthly, alternated with one cycle of ABVD (alternating regimen), and 204 patients received one-half cycle of MOPP alternated with one-half cycle of ABVD within a 1-month period (hybrid regimen). RESULTS: The complete remission (CR) rate was 91% with the alternating regimen and 89% with the hybrid regimen. At 10 years, the freedom-from-progression (FFP) rate was 67% versus 69% and the overall survival (OS) rate was 74% versus 72%, respectively. After attainment of CR, 85 patients relapsed in nodal (n = 60) versus extranodal with or without nodal (n = 25) sites. In patients given consolidative radiation because of bulky lymphoma, the true recurrence rate was 13%. A total of 23 second malignancies (6%) were documented, including 11 cases of acute nonlymphocytic leukemia. No cases of congestive heart failure attributable to doxorubicin or pulmonary toxicity related to bleomycin were documented. CONCLUSION: By delivering MOPP and ABVD, it is possible to cure approximately 70% of patients with advanced Hodgkin's disease. The two different drug sequences yielded superimposable results.

Adolescent↗
PubMed1997

Alternating MOPP and ABVD chemotherapy plus mantle-field radiation therapy in patients with massive mediastinal Hodgkin's disease.

PURPOSE: To evaluate the efficacy and toxicity of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy plus mantle-field radiation therapy in the treatment of patients with massive mediastinal Hodgkin's disease of any stage. PATIENTS AND METHODS: Eighty patients presented with Hodgkin's disease and a mediastinal mass greater than one third the greatest chest diameter on chest radiograph. Patients were staged and treated with MOPP alternated with ABVD chemotherapy for a total of six cycles. Patients then received 10 Gy mantle-field radiation therapy delivered to the original extent of disease followed by 25 to 35 Gy to the residual abnormalities. RESULTS: The complete response (CR) rate was 89%. With a median follow-up duration of 10 years, disease-free survival of the complete responders is 78% at 15 years and overall survival is 75% at 15 years. For patients with stage I or II disease, disease-free survival was 76% at 15 years and overall survival was 79%; for those with stage III or IV disease, disease-free survival was 82% at 15 years and overall survival was 64%. Age, stage, sex, B symptoms, number of extranodal sites, lactate dehydrogenase (LDH) levels, erythrocyte sedimentation rate, and platelet count did not influence treatment outcome. Treatment-related pneumonitis was noted in 16% of patients (fatal in one), mainly in those older than age 35 years who received total doses of radiation therapy greater than 42 Gy. Fertility is more often preserved with MOPP/ABVD therapy than with MOPP chemotherapy and there appears to be less pulmonary and cardiac disease than with ABVD chemotherapy. Two patients have developed second solid tumors within radiation ports and one relapsed patient developed acute leukemia after MOPP salvage therapy. CONCLUSION: MOPP/ABVD followed by mantle-field radiation therapy is an effective treatment for all stages of Hodgkin's disease that present with a large mediastinal mass. Our data suggest that the large mediastinal mass is a more dominant determinant of prognosis than Ann Arbor stage or other clinical prognostic factors.

Adolescent↗
PubMed1997

Treatment of advanced Hodgkin's disease with chemotherapy--comparison of MOPP/ABV hybrid regimen with alternating courses of MOPP and ABVD: a report from the National Cancer Institute of Canada clinical trials group.

PURPOSE: This randomized, prospective trial compares outcomes for patients with advanced Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, and vinblastine (ABV) hybrid regimen or alternating MOPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). METHODS: Three hundred one patients with advanced Hodgkin's disease were randomized to receive MOPP/ ABV hybrid regimen or alternating MOPP/ABVD after stratification for prior treatment, B symptoms, and treatment center. Eligible patients were either previously untreated and found to have stage IIIB, IVA, or IVB disease or previously treated with wide-field irradiation. Responding patients received a minimum of eight cycles of chemotherapy. Those with residual disease in a localized region received irradiation between the sixth and seventh cycle of treatment. RESULTS: Response rates to the two regimens were similar. Five-year overall survival rates were 81% and 83% for MOPP/ABV hybrid and alternating MOPP/ ABVD, respectively (P = .74; 95% confidence interval [CI] for the difference, -11% to 7%). Five-year failure-free survivals were 71% and 67% for MOPP/ABV hybrid and alternating MOPP/ABVD, respectively (P = .87; 95% CI for the difference, -9% to 17%). Significantly more episodes of febrile neutropenia and stomatitis were observed with the MOPP/ABV hybrid regimen; there was no significant difference in fatal toxicity. Patients with predefined, high-quality partial responses (PR-1s) had results similar to those with complete responses (CRs). Planned subset analysis showed no significant difference in outcome between the two arms of the trial for patients with newly diagnosed disease (5-year failure-free survival rates were 70% for MOPP/ABV hybrid and 59% for alternating MOPP/ABVD; P = .180), but superiority of alternating MOPP/ABVD for patients with prior irradiation (5-year failure-free survival 94% v 73%; P = .017). CONCLUSION: MOPP/ABV hybrid and alternating MOPP/ABVD regimens are equally effective for patients with advanced Hodgkin's disease.

Actuarial Analysis↗
PubMed1997

Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal radiation therapy in the treatment of stages IIB, IIIA2, IIIB, and IV Hodgkin's disease in pediatric patients: a Pediatric Oncology Group study.

PURPOSE: To determine whether the addition of low-dose total-nodal irradiation (TNI) in pediatric patients with advanced-stage Hodgkin's disease who have received eight cycles of alternating mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) will improve the event-free survival (EFS) and overall survival (OS) when compared with patients who have received chemotherapy only. PATIENTS AND METHODS: At diagnosis, 183 children and adolescents with stages IIB, IIIA2, IIIB, and IV Hodgkin's disease were randomized to receive eight cycles of alternating MOPP-ABVD with or without low-dose TNI. RESULTS: Of 183 patients, four were rendered ineligible before treatment was initiated. One hundred sixty-one of 179 patients (90%) were in complete remission (CR) at the completion of eight cycles of alternating MOPP-ABVD; 81 were in the chemotherapy-only group and proceeded to observation off therapy, whereas 80 of 161 were to receive combined modality therapy (CMT). Nine of 80 patients randomized at the time of diagnosis to receive CMT did not receive radiation (RT) because of a protocol violation, but were monitored for EFS and OS and included in all analyses. The estimated EFS and OS rates at 5 years for the 179 eligible patients are 79% and 92%, respectively. The actuarial EFS at 5 years was 80% for patients who received CMT and 79% for patients who received MOPP-ABVD only. The OS for the former group is estimated to be 87% and for the latter patients 96%. Age < or = 13 years of age at diagnosis and the attainment of a clinical CR after three cycles of chemotherapy were associated with a statistically significant improved EFS. CONCLUSION: Our results indicate that after the delivery of eight cycles of MOPP-ABVD, the addition of low-dose RT does not improve the estimated EFS or OS in pediatric patients with advanced-stage Hodgkin's disease.

Adolescent↗
PubMed1998

MOPP/ABV hybrid chemotherapy for advanced Hodgkin's disease significantly improves failure-free and overall survival: the 8-year results of the intergroup trial.

PURPOSE: To compare the efficacy of sequential mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) followed by doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus the MOPP/ABV hybrid regimen in advanced-stage Hodgkin's disease. PATIENTS AND METHODS: A total of 737 patients with previously untreated stages III2A, IIIB, IVA, or IVB Hodgkin's disease and patients in first relapse after radiotherapy were prospectively randomized to sequential MOPP-ABV or MOPP/ABV hybrid. Of 691 eligible patients, 344 received the sequential regimen and 347 received the hybrid. RESULTS: The overall response rate was 95%, with complete responses (CRs) in 79%: 83% on the MOPP/ABV hybrid and 75% on the sequential MOPP-ABVD arm (P = .02). With a median follow-up time of 7.3 years, the 8-year failure-free survival (FFS) rates were 64% for MOPP/ABV hybrid and 54% far sequential MOPP-ABVD (P = .01; 0.69 relative risk of failure, comparing MOPP/ABV hybrid v MOPP-ABVD). The 8-year overall survival rate was significantly better for the MOPP/ABV hybrid (79%) as compared with sequential MOPP-ABVD (71%) (P = .02; relative risk, 0.65). MOPP/ABV hybrid had significantly more life-threatening or fatal neutropenia and pulmonary toxicity than the sequential MOPP-ABVD arm, which was associated with significantly greater thrombocytopenia. Nine cases of acute myelogenous leukemia or myelodysplasia were reported on the sequential regimen as compared with only one on the hybrid (P = .01). CONCLUSION: MOPP/ABV hybrid chemotherapy was significantly more effective than sequential MOPP-ABVD. FFS and overall survival were significantly improved on the hybrid arm, which was also associated with a lower incidence of acute leukemia or myelodysplasia.

Adolescent↗
PubMed1998

MOPP or radiation in addition to ABVD in the treatment of pathologically staged advanced Hodgkin's disease in children: results of the Children's Cancer Group Phase III Trial.

PURPOSE: A randomized trial designed to compare mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, vinblastine, and daccarbazine (ABVD) (regimen A) with ABVD plus low-dose regional (extended-field) radiation therapy (EF RT) (regimen B) for the treatment of children and adolescents with stages III and IV Hodgkin's disease was conducted by the Children's Cancer Group (CCG-521) from 1986 until 1990. PATIENTS AND METHODS: One hundred eleven eligible patients were randomized, 57 to regimen A and 54 to regimen B. All patients had pathologically verified stage III or stage IV Hodgkin's disease. RESULTS: Overall survival (S) is 87% at 4 years and event-free survival (EFS) is 82%. Patients randomized to ABVD plus EF RT have a 4-year EFS of 87% compared with 77% for patients randomized to MOPP/ABVD (P = .09, two-sided). Patients randomized to ABVD plus EF RT have a 4-year S of 90% compared with 84% for patients randomized to MOPP/ABVD (P = .45, two-sided). Significant prognostic factors in multivariate analysis for EFS are stage of disease, erythrocyte sedimentation rate (ESR) at diagnosis, liver size at diagnosis, and, among stage III patients, the size of the mediastinal mass at diagnosis. The acute toxicities of treatment are largely hematopoietic in nature, whereas acute pulmonary and cardiac toxicities are modest and not limiting. CONCLUSION: The results of this study show that, in advanced-stage Hodgkin's disease in children, equivalent results can be obtained by the addition of either MOPP or low-dose EF RT to the ABVD regimen; whether the addition of either contributes to outcome was not addressed in this study and will require additional testing. It is clear, however, that MOPP chemotherapy can safely be eliminated from front-line combination chemotherapy regimens for advanced Hodgkin's disease in pediatric patients.

Adolescent↗
PubMed1998

Phase II trial of nitrogen mustard, vincristine, and procarbazine in patients with recurrent glioma: North Central Cancer Treatment Group results.

PURPOSE: Previous investigators have reported responses in 52% of patients treated with mechlorethamine (nitrogen mustard), vincristine, and procarbazine (MOP) for recurrent glioma. To confirm these promising results, we conducted a phase II prospective study. PATIENTS AND METHODS: Sixty-three patients with histologic confirmation of recurrent glioma were treated with the MOP regimen. Patients with or without prior chemotherapy received nitrogen mustard 3 mg/m2 or 6 mg/m2, respectively, intravenously on days 1 and 8 plus vincristine 2 mg/m2 intravenously on days 1 and 8, and procarbazine 100 mg/m2 orally on days 1 to 14. Cycles were repeated every 28 days. RESULTS: Of 61 patients assessable for response, eight responded (13%), with one complete response (CR). Responses were as follows: low-grade gliomas, 19%; anaplastic astrocytomas, 11%; anaplastic oligodendrogliomas or oligoastrocytomas, 25%; and glioblastomas, 4.3%. The most common toxicity was myelosuppression with leukocyte nadirs less than 1,000/microL in 23% and platelet nadirs less than 25,000/microL in 13% of patients. Two patients died of infection in the setting of neutropenia. Nonhematologic toxicity included neurosensory changes in 21% of patients (severe in 3%) and severe dermatologic reactions in 8%. In multivariate analysis, Eastern Cooperative Oncology group (ECOG) performance status (PS) was the best predictor for response to chemotherapy (P=.01) and time to progression (P=.008), while PS and grade were the most important predictors of survival (P=.002 and .05, respectively). CONCLUSION: This study did not confirm the high response rate previously reported in recurrent gliomas. Patients with recurrent anaplastic oligodendrogliomas or oligoastrocytomas and recurrent low-grade gliomas had the highest response rates (25% and 19%, respectively). In multivariate analysis, ECOG PS was the best predictor of response, while PS and tumor grade were the most important predictors of survival.

Adult↗
PubMed1999

Testicular function after cytotoxic chemotherapy: evidence of Leydig cell insufficiency.

PURPOSE: To evaluate testicular function in men after treatment with cytotoxic chemotherapy. PATIENTS AND METHODS: We measured testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels in 209 men after treatment with mechlorethamine, vinblastine, procarbazine, and prednisone, hybrid chemotherapy, or high-dose chemotherapy and in 54 healthy age-matched controls. RESULTS: The mean age of the patients was 38 years (range, 19 to 68 years), and all patients had received chemotherapy between 1 and 22 years previously. Patients had significantly higher mean LH (7.9 v 4.1 IU/L; P < .0001) and FSH levels (18.8 v 3.1 IU/L; P < .0001) than controls. There was no significant difference in mean total testosterone level between the patients and controls, but there was a trend toward a lower mean testosterone/SHBG ratio in the patients (0.63 v 0.7; P = .08). Analysis of the hormonal parameters using a model that allowed for the effects of increasing age on testicular function showed evidence of significant recovery of gonadal function in the first 10 years after treatment. Fifty-two percent of patients had LH levels at or above the upper limit of normal, and 32% of patients had increased LH with testosterone levels in the lower half of the normal range, suggesting a degree of Leydig cell impairment. CONCLUSION: In a significant proportion of men, there is good evidence of Leydig cell dysfunction after cytotoxic chemotherapy. The clinical significance of this Leydig cell dysfunction is not clear, but some of these men may benefit from testosterone replacement. Further studies are warranted.

Adult↗
PubMed2001

Lung cancer after Hodgkin's disease: a nested case-control study of the relation to treatment.

PURPOSE: To investigate the causes of the raised risk of lung cancer in patients who have had Hodgkin's disease, and in particular the relationship to treatment. PATIENTS AND METHODS: A nested case-control study was conducted within a cohort of 5,519 patients with Hodgkin's disease treated in Britain during 1963 through 1993. For 88 cases of lung cancer and 176 matched control subjects, information on treatment and other risk factors was extracted from hospital case-notes, and odds ratios for lung cancer in relation to these factors were calculated. RESULTS: Risk of lung cancer was borderline significantly greater in patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy than those who did not receive this treatment (relative risk [RR] = 1.66; 95% confidence interval [CI], 0.99 to 2.82), and increased with number of cycles of MOPP (P =.07). Exclusion of lung cancers for which histologic confirmation was not available strengthened these associations (RR = 2.41; 95% CI, 1.33 to 4.51; P =.004 for any MOPP and P =.007 for trend with number of cycles of MOPP). Risks were not raised, however, after chlorambucil, vinblastine, procarbazine, and prednisone treatment. There was evidence that the raised risk of lung cancer occurring in relation to radiotherapy was restricted to histologies other than adenocarcinoma. CONCLUSION: The results suggest that MOPP chemotherapy may lead to elevated risk of lung cancer, at least in certain subgroups of patients. The role of chemotherapy in the etiology of lung cancer after Hodgkin's disease deserves further investigation.

Adult↗
PubMed2003

Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial.

PURPOSE: In a series of trials, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV) have been identified as effective treatments for Hodgkin's disease. We compared these regimens as initial chemotherapy for Hodgkin's disease. PATIENTS AND METHODS: Adult patients (N = 856) with advanced Hodgkin's disease were randomly assigned to treatment with ABVD or MOPP/ABV. The major end points were failure-free and overall survival, life-threatening acute toxicities, and serious long-term toxicities, including cardiomyopathy, pulmonary toxicity, myelodysplastic syndromes (MDS), and secondary malignancies. RESULTS: The rates of complete remission (76% v 80%, P =.16), failure-free survival at 5 years (63% v 66%, P =.42), and overall survival at 5 years (82% v 81%, P =.82) were similar for ABVD and MOPP/ABV, respectively. Clinically significant acute pulmonary and hematologic toxicity were more common with MOPP/ABV (P =.060 and.001, respectively). There was no difference in cardiac toxicity. There were 24 deaths attributed to initial treatment: nine with ABVD and 15 with MOPP/ABV (P =.057). There have been 18 second malignancies associated with ABVD and 28 associated with MOPP/ABV (P =.13). Thirteen patients have developed MDS or acute leukemia: 11 were initially treated with MOPP/ABV, and two were initially treated with ABVD but subsequently received MOPP-containing regimens and radiotherapy before developing leukemia (P =.011). CONCLUSION: ABVD and the MOPP/ABV hybrid are effective therapies for Hodgkin's disease. MOPP/ABV is associated with a greater incidence of acute toxicity, MDS, and leukemia. ABVD should be considered the standard regimen for treatment of advanced Hodgkin's disease.

Adult↗
PubMed2005

New treatment options have changed the survival of patients with follicular lymphoma.

BACKGROUND: The natural history of follicular lymphoma is believed not to have changed over the last 30 years. Median survivals have ranged from 7 to 10 years, and the disease is considered incurable. However, multiple new treatment options have been developed in the last decade, and their impact on survival of follicular lymphoma remains unknown. PATIENTS AND METHODS: In the current analysis, we identified all previously untreated, advanced-stage, follicular lymphoma patients treated with the following three sequential treatment approaches: cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy +/- nonspecific immunostimulants (Southwest Oncology Group [SWOG] 7426 and 7713: 1974 to 1983); prednisone, methotrexate, doxorubicin, cyclophosphamide, and etoposide (ProMACE) plus mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) +/- interferon (SWOG 8809: 1988 to 1994); and CHOP followed by monoclonal antibody (MoAb) therapy (SWOG 9800 and 9911: 1998 to 2000). We assessed the patients' progression-free survival (PFS) and overall survival (OS). The MoAb trials included CHOP followed by rituximab (SWOG 9800) and CHOP followed by (131)I-tositumomab (SWOG 9911). RESULTS: The PFS curves for the CHOP and ProMACE-MOPP studies are overlapping, with 4-year PFS estimates of 46% and 48%, respectively. However, the PFS rate of the CHOP + MoAb studies is significantly improved at 61% (P = .005). The OS curves show improvement with each succeeding study. The 4-year estimate of OS is 69% for the CHOP regimens, 79% for the ProMACE-MOPP study, and 91% for the CHOP + MoAb regimens (P < .001). These conclusions were retained after adjusting for differences in prognostic factors between the study groups. CONCLUSION: The results of this study suggest that OS for patients with follicular lymphoma has improved over time and that the choice of initial therapy may matter.

Adolescent↗
PubMed2006

Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials.

PURPOSE: In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control. PATIENTS AND METHODS: Patients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT. RESULTS: Median follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P < .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175). CONCLUSION: A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.

Adolescent↗