MOPP/ABV hybrid program: combination chemotherapy based on early introduction of seven effective drugs for advanced Hodgkin's disease

Seventy patients with advanced Hodgkin's disease, 54 with new disease, and 16 in first relapse after initial radiotherapy, have been treated with a seven-drug, 8-month program: MOPP (nitrogen mustard, vincristine, procarbazine, prednisone)/ABV (Adriamycin [Adria Laboratories of Canada, Mississauga, Ontario], bleomycin, vinblastine) hybrid. A single involved field of radiotherapy was given to selected partial responders after 6 months of chemotherapy. Forty-six of the 52 (88%) evaluable new-disease patients and 14 of the 16 (87%) evaluable patients with relapsing disease reached a complete response. The actuarial overall survival at 49 months for the patients with new disease was 90% (median follow-up from diagnosis was 27 months). For the patients with relapsing disease, the actuarial survival at 54 months was 79% (median follow-up from diagnosis was 27 months). The actuarial relapse-free survival at 41 months for complete responders was 93% for patients with new disease (median follow-up after treatment was 20 months) and 80% for those with relapsing disease (median follow-up after treatment was 27 months). Toxicity was moderate, with two treatment-related deaths and eight episodes of serious infection. These results compare favorably with the best results reported in the literature. Furthermore, they were achieved with a moderate level of toxicity, high drug delivery rates, and a relatively short duration of treatment. The efficacy and toxicity data of the MOPP/ABV hybrid program will now be evaluated in a prospectively randomized multicenter study.     

MOPP treatment of resistant Hodgkin's disease following ABVD failure

Fourteen patients with Hodgkin's disease resistant to ABVD were treated with MOPP chemotherapy (nitrogen mustard, vincristine, procarbazine, prednisone). Complete remission was obtained in 6 patients (43%). Four of the 6 complete responders are disease free after 5, 20, 23, 35 months. The actuarial median survival after MOPP of all patients is 20 months. These data confirm that there is no "cross-resistance" among the drugs included in the two schedules.     

Fixed versus response-adapted MOPP/ABVD chemotherapy in Hodgkin's disease: A prospective randomized trial

BACKGROUND: The optimal number of chemotherapy courses in responding patientswith advanced-stage Hodgkin's disease (HD) is unknown PATIENTS AND METHODS: With minimizing chemotherapy and thereby reducing late complicationsas the objective, patients with advanced HD were randomizedto receive either 4 full MOPP/ABVD courses or treatment up tocomplete remission (CR). Forty-seven patients were given thefixed (FT) and 41 patients the individual treatment (IT). Thetwo groups were balanced according to age, histopathology andsex, although stage IVB dominated in the IT group (20 vs. 8) RESULTS: Sixty-six of 88 patients (75%) achieved CR. No difference betweenthe two treatment groups in the proportion of stage FVB patientswas seen when those achieving CR, i.e., the efficacy populationwere compared. The mean number of single chemotherapy coursesgiven was 3.7 of MOPP and 3.5 of ABVD in the FT group, comparedto 2.6 of MOPP and 2.5 of ABVD in the IT group (p < 0.001).The predicted progression-free survival at 10 years was 81%in the FT and 68% in the IT arm, respectively (p < 0.05).No statistically significant difference in cause-specific 10-yearsurvival was observed (82% and 83%, respectively; p = 0.18).Long-standing CRs were achieved following minimal chemotherapy. CONCLUSIONS: Since there are no available methods to identify long-term disease-freesurvivors among CR patients following a limited induction treatment,we suggest that the policy of giving 3–4 full MOPP/ABVDcourses should continue. The price for such an approach is theovertreatment of a subset of already cured patients. chemotherapy, Hodgkin's disease, induction treatment, MOPP-ABVD, randomized trial     

Four cases of Hodgkin's disease treated with MOPP/ABV hybrid regimen using nitrogen mustard-N-oxide hydrochloride]

Four patients with fresh Hodgkin's disease were treated with MOPP/ABV hybrid regimen using nitrogen mustard-N-oxide hydrochloride (NH2-O). All patients responded well to this therapy and achieved complete remission. Toxicity was minimum except for an older patient. He was 70 years old and developed arrhythmia after MOPP therapy but recovered without any treatment. The continuation of therapy was possible by dose reduction in this case. We conclude MOPP/ABV regimen using NH2-O is valuable for the treatment of Hodgkin's disease.     

Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial.

BACKGROUND: The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomycin-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD). PATIENTS AND METHODS: Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy. RESULTS: Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis CONCLUSION: The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD.     

Two different schedules for integrating filgrastim as adjuvant therapy in the treatment of patients with advanced stage Hodgkin's lymphoma receiving MOPP/ABV hybrid chemotherapy

Purpose: Management of advanced-stage Hodgkin's disease with a MOPP/ABV hybrid regimen (mechlorethamine, vincristine, procarbazine, prednisone, Adriamycin, bleomycin and vinblastine) has yielded a high complete response rate (75–85%). However, myelosuppression can limit delivery of treatment. Filgrastim has been shown to reduce chemotherapy-related neutropenia and allow for on-time administration of planned doses of chemotherapeutic agents. The objective of this study was to find the best way to integrate filgrastim with the MOPP/ABV hybrid regimen. Methods: Enrolled in this study were 24 patients (aged 18–52 years) with newly diagnosed, histologically documented Hodgkin's disease. In schedule I, patients received filgrastim (5 μg/kg s.c. daily) beginning on day 9, 24 h after administration of ABV. In schedule II, patients received filgrastim concomitantly with procarbazine on days 2–7 (starting 24 h after day-1 MOPP administration and stopping 24 h before ABV administration) as well as after ABV beginning on day 9. Filgrastim after ABV administration was administered until two consecutive ANC readings of 10 × 10⁹/l were achieved. Results: All patients were able to complete all six cycles of therapy. There was a trend to fewer dose reductions in schedule II (0.76%) as compared to schedule I (4.2%) with a P-value of 0.077 (chi-squared test). Specifically, 11.6% of MOPP courses and 5.5% of ABV courses were dose-reduced in schedule I versus 1.7% and 1.4%, respectively, in schedule II. Conclusion: In conclusion, filgrastim was effective in supporting the delivery of the MOPP/ABV chemotherapy. Concomitant administration of filgrastim with procarbazine (days 2–7) appears to be safe and allows the maximum dose intensity of this therapy. Received: 20 May 1998 / Accepted: 3 September 1998     

ABVD and radiation therapy as first-line treatment in advanced Hodgkin's disease

The purpose of this study was to evaluate the efficacy of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and radiotherapy in advanced Hodgkin's disease. In addition, to evaluate whether patients with slow responding tumors could profit from the early change of treatment regimen [MOPP (mechloretamine, vincristine, procarbazine, and prednisone)] followed by radiation therapy or autologous bone marrow transplantation (ABMT). Finally, to evaluate treatment options for patients with both early and late relapses. A total of 78 patients with previously untreated stages IIA bulky, IIB, III (A and B), and IV (A and B) Hodgkin's disease were treated with the ABVD regimen followed by radiotherapy. Patients with stages IIIB and IV (A and B) were re-staged after 4 ABVD courses of the treatment: slow responders (response less than 70%) underwent second-line treatment (MOPP) and eventually ABMT. Relapsed patients with a long initial complete response (> or = 12 months) were treated with second-line conventional treatment and those patients with a short initial complete response (< 12 months) underwent ABMT. The complete response (CR) rate was 91% after ABVD and radiation therapy. An additional 5 stage IIIB and IV patients whose therapy was switched after 4 cycles because of a slow response obtained a CR (3 after 2 MOPP courses plus radiotherapy and 2 after 2 MOPP courses followed by ABMT). Including these additional CRs, the overall CR rate was 97%. No episodes of clinical cardiopulmonary toxicity were observed. With a median follow-up time of 42 months, the 4-year relapse-free survival was 87%. The 4-year overall survival was 96%. Ten cases relapsed: all but one obtained a second CR with different approaches depending on the timing of relapse. The ABVD regimen appears to be effective and well tolerated confirming the validity of this four-drug regimen in the treatment of advanced Hodgkin's disease. In addition, therapeutic choices based on the timing of the relapse and the use of re-staging after 4 cycles in order to identify slow responders can play an important role in increasing the number of cured patients.     

Comparison of psychosocial adaptation and sexual function of survivors of advanced Hodgkin disease treated by MOPP, ABVD, or MOPP alternating with ABVD.

BACKGROUND. Survivors of advanced Hodgkin disease, who were assigned randomly to treatment by mechlorethamine, vincristine, procarbazine, and prednisone (MOPP); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); or MOPP alternating with ABVD in a clinical trial of the Cancer and Leukemia Group B (protocol 8251), were compared in terms of their psychosocial adaptation and psychosexual function an average of 2.2 years after completion of treatment (range, 1-5 years). The study was undertaken to determine if there were differences among treatments in these functional areas as a consequence of differential long-term gonadal damage in the three regimens. METHODS. Ninety-three disease-free survivors of advanced Hodgkin disease (56 men and 37 women) were studied (a minimum of 1 year after completion of treatment) by an interview conducted over the telephone. Standardized measures were used to assess their psychologic, sexual, family, and vocational functioning, including the following tests: the Psychosocial Adjustment to Illness Scale--Self Report, the Brief Symptom Inventory, the Profile of Mood States, and the Impact of Event Scale. RESULTS. Contrary to expectation, no statistically significant differences in survivors' psychosocial adaptation or psychosexual function were found by treatment arm. Infertility (based on survivors' reports of medical test results and perceptions) and lower income 1 year before the diagnosis of cancer were significant predictors of poorer adjustment. Most survivors reported a range of problems that they attributed to having had cancer: 35%, proven or perceived infertility; 24%, sexual problems; 31%, health and life insurance problems; 26%, a negative socioeconomic effect; and 51%, conditioned nausea, associated with visual or olfactory reminders of chemotherapy. CONCLUSIONS. No significant long-term advantage in psychosocial adaptation or psychosexual function was found for survivors of Hodgkin disease treated by the less gonadally toxic ABVD regimen 1 to 5 years after completion of treatment.     

Treatment of advanced Hodgkin's disease with B-CAVE following MOPP failure.

Between March 1973, and December 1976, 22 patients who developed disease progression during or after MOPP therapy were treated with a new combination, B-CAVe (Bleomycin 5 mg/m2 iv days 1, 28, 35; CCNU 100 mg/m2 po day 1; adriamycin 60 mg/m2 iv day 1; and vinblastine 5 mg/m2 iv day 1). Objective responses were achieved in 17 of 22 patients (77%) and 11 of 22 responses were complete (50%). The actuarial survival for all patients is 16.4 months. For complete responders the median is 24 months with 2 complete responders dead without evidence of Hodgkin's Disease. Median relapse free survival for complete responders has not been reached at 35+ months while that for partial responders is 14 months. Significant adriamycin cardiotoxicity was encountered in two patients. There were no life threatening bacterial infections during B-CAVe. Two patients died of Pneumocystis carinii several months after cessation of therapy. B-CAVe is effective in the therapy of advanced Hodgkin's disease after MOPP failure, and this regimen is comparable to other previously reported MOPP salvage combinations.     

Assessment of cardiac and pulmonary function in adult patients with Hodgkin's disease treated with ABVD or MOPP/ABVD plus adjuvant low-dose mediastinal irradiation

We evaluated the long-term effects of combined modality therapy (CMT) with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) or mechlorethamine, vincristine, prednisone, procarbazine (MOPP)/ABVD plus adjuvant low-dose (< 30 Gy) involved-field radiation therapy (LDRT) on cardiac and pulmonary functions in adult patients with Hodgkin's disease (HD). Adjuvant LDRT (mean dose, 2340 cGy) to the mediastinum was administered to 24 patients after chemotherapy with MOPP/ABVD (n = 10) and ABVD (n = 14). The mean doses of doxorubicin and bleomycin were 233 mg/m2 and 92 IU/m2, respectively. Cardiac and pulmonary function tests were performed in all patients and, when available, were compared with pretreatment studies. After a median follow-up of 6.3 years, none of the patients had cardiac or pulmonary symptoms. A 4.7% overall decrease in left ventricular ejection fraction (LVEF) was observed (p = 0.03), but only one patient had a mildly decreased LVEF (47%). Diastolic function, LVEF, and left ventricular volume remained within the normal range in the other 23 patients. Mild pulmonary function study abnormalities occurred in 8 of 24 patients, 6 of whom were cigarette smokers. There were no significant changes in total lung capacity and forced vital capacity (FVC) values, but there was a 3% overall decrease in FEV1/FVC ratio (p = 0.05). In adult patients with HD, adjuvant LDRT after chemotherapy with ABVD or MOPP/ABVD did not result in a significant incidence of permanent pulmonary or cardiac toxicity after more than 6.3 years of median follow-up. Further studies are warranted to fully evaluate the impact of such therapy on cardiopulmonary function.     

Treatment of advanced Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) after failure of MOPP therapy.

From June 19, 1975 to December 22, 1976, twenty-seven patients with advanced Hodgkin's disease who failed MOPP (nitrogen mustard, vincristine, procarbazine and prednisone) were treated with adriamycin, bleomycin, vinblastine, and imidazole carboxamide, (ABVD). Complete response (CR) was achieved in 22% of patients and partial response was achieved in 15%. No response was observed in 63% of patients. With a median duration of follow-up for CR patients of only 10.5 months, two of the six CR patients have already relapsed. In this series of patients ABVD was not an effective curative regimen for patients with Hodgkin's disease who have failed MOPP.     

Comparison of MOPP versus ABVD as salvage therapy in patients who relapse after radiation therapy alone for Hodgkin's disease.

BACKGROUND: The aim of this study was to determine salvage outcome in patients with Hodgkin's disease who relapse after radiation therapy, and to compare the efficacy of mechlorethamine, Oncovin, procarbazine and prednisone (MOPP) versus Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) as salvage treatment. PATIENTS AND METHODS: One hundred patients with Hodgkin's disease (97 with stage I-II disease at presentation) who relapsed after radiation therapy alone were salvaged with either MOPP or ABVD. Freedom from second relapse (FFSR) and overall survival (OS) were determined, and prognostic factors for salvage outcome were evaluated. RESULTS: The median follow-up time since salvage therapy was 12 years. The 10-year FFSR and OS rates were 70% and 89%, respectively. Forty-one patients were salvaged with MOPP and 59 received ABVD. The type of salvage chemotherapy did not significantly influence FFSR or OS. Age >50 years at initial diagnosis was the only significant predictor for an inferior FFSR and OS on both univariate and multivariate analyses. CONCLUSIONS: The two salvage regimens of MOPP and ABVD had similar efficacy in this group of patients with predominantly early-stage disease at initial radiation therapy. The inferior salvage outcome in patients aged >50 years is a contributing factor to the overall poor prognosis of patients presenting with Hodgkin's disease at an older age.     

Treatment of advanced-stage Hodgkin's disease: alternating noncrossresistant MOPP/CABS is not superior to MOPP.

One hundred twenty-five assessable patients with advanced-stage Hodgkin's disease were randomized to receive mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or MOPP alternating with lomustine (CCNU), doxorubicin, bleomycin, and streptozocin (CABS). The median follow-up is 7.7 years. The complete response rate was 60 of 66 MOPP-treated patients (91%) and 54 of 59 MOPP/CABS-treated patients (92%) (difference not significant). The level of the disease-free survival curve at longest follow-up is 65% for MOPP-treated patients and 72% for MOPP/CABS-treated patients (difference not significant). The overall survival at 12 years is projected at 68% for MOPP-treated patients and 54% for MOPP/CABS-treated patients (difference not significant). Thus, there were no significant differences in efficacy between MOPP and MOPP/CABS. However, MOPP/CABS was more emetogenic than MOPP, and four MOPP/CABS-treated patients went on to develop secondary acute leukemia. No MOPP-treated patients developed leukemia. High initial erythrocyte sedimentation rate (ESR) and high platelet counts adversely affected treatment outcome. MOPP-treated patients who received greater than 81% of the projected dose intensity of vincristine over the first three cycles had significantly improved disease-free survival rates over those receiving less than 81%. MOPP/CABS-treated patients who received greater than 82% of the projected dose intensity of vincristine had significantly better overall survival than those who received less than 82%. Disease-free survival on both arms was significantly better in patients who received greater than 84% of the projected dose intensity of all agents. The effect of dose intensity was particularly apparent in patients with poor prognostic factors where those who received greater than 84% of the projected dose intensity of all agents had significantly improved disease-free and overall survival.     

Fatal necrosis of the liver during ABVD chemotherapy for Hodgkin's disease. A case report

A case of massive fatal liver necrosis during chemotherapy for stage IVA Hodgkin's disease is described. A previously healthy 50-year-old male was given doxorubicin 25 mg/m2, bleomycin 10 mg/m2 and vinblastine 6 mg/m2 on days 1 and 14 of the cycle combined with dacarbazine 150 mg/m2 on days 1-5 (ABVD) with 4-week intervals. During the fourth cycle of chemotherapy the patient developed fatal liver necrosis with anuria and uncontrolled bleeding. At autopsy, 80% of the liver was necrotic and viable cells were seen only in periportal areas. Dacarbazine may have caused the necrosis. Liver necrosis caused by drugs should be considered if unexplained hepatomegaly and a rise in serum liver enzyme levels is noted during ABVD treatment.     

Hodgkin's disease in children: treatment with low dose radiation and MOPP without staging laparotomy: a preliminary report.

Twenty-seven children with previously untreated Hodgkin's disease (CS I-2, II-13, III-3, IV-9) were given three cycles of MOPP to induce a remission which was consolidated with extended field radiation (2000--3500 rad) and three cycles of MOPP. Surgical staging was discontinued. Twenty-five of 27 children have not relapsed (range 15+--64+ months; median 39+ months); two children have died, one of uncontrolled Hodgkin's disease and one of acute infection while in complete remission. Actuarial 3 and 5 year survival rates and relapse-free rates are 91%. The merits of this treatment approach are discussed.     

Long-term results of combined chemotherapy-radiotherapy approach in Hodgkin's disease: superiority of ABVD plus radiotherapy versus MOPP plus radiotherapy

In an attempt to reduce some of the delayed sequelae associated with combined modality therapy in Hodgkin's disease, we randomly tested stages IIB, IIIA, and IIIB MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) v ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine). In 232 previously untreated patients, three cycles of either combination preceded and followed extensive irradiation. The complete remission rate was 80.7% following MOPP and 92.4% following ABVD (P less than .02). The 7-year results indicated that ABVD was superior to MOPP in terms of freedom from progression (80.8% v 62.8%; P less than .002), relapse-free survival (87.7% v 77.2%; P = .06), and overall survival (77.4% v 67.9%; P = .03). Moreover, the comparative iatrogenic morbidity showed that irreversible gonadal dysfunction as well as acute leukemia occurred only in patients subjected to MOPP, while cardiopulmonary studies failed to document significant laboratory differences between the two treatment groups. Present findings indicate that ABVD followed by extensive irradiation represents a valid therapeutic alternative to the widely used alkylating agent-containing regimens plus radiotherapy.     

Recovery of spermatogenesis after treatment for Hodgkin's disease: limiting dose of MOPP chemotherapy

The sperm production of 25 patients with Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was studied retrospectively. All but two patients also received radiotherapy treatment to pelvic and/or non-pelvic fields. Sperm counts were obtained from patients treated either with three or fewer (MOPP-2 group) or with five or more (MOPP-6 group) chemotherapy cycles. Recovery of spermatogenesis following treatment-induced azoospermia was significantly higher among the MOPP-2 patients (Mann-Whitney rank sum test, p = 0.001). Patients in this group who did not receive pelvic irradiation appeared to have greater recovery rates (p = 0.06). The results suggest that three cycles of MOPP chemotherapy represent a maximum exposure compatible with the recovery of spermatogenesis.     

Two cycles of MOPP and radiotherapy: effective treatment for stage IIIA and IIIB Hodgkin's disease

Two cycles of MOPP (mechlorethamine, vincristine (Oncovin), procarbazine, prednisone) and radiotherapy were used to treat 197 patients with stage III Hodgkin's disease. Prior to 1980, radiotherapy was delivered to the mantle, abdomen and pelvis; thereafter, pelvic irradiation was deleted for patients with stage III1 disease. Complete remission rates for IIIA and IIIB presentations were 91% and 89%. The 10-year freedom from tumor mortality (FTM) rate for all patients was 81%; for IIIA, it was 87% and for IIIB, it was 72%. Results were not significantly affected by gender, age, pathology, or deletion of pelvic radiotherapy. However, a subgroup of 28 patients with a tumor burden that included pelvic disease who also had B symptoms was identified as having a poor prognosis. Their FTM was 43%, compared with 87% for all other patients combined (P = 0.002). Based on this analysis, we conclude that limited chemotherapy in combination with radiation therapy can yield results similar to programs that use more chemotherapy for all patients with IIIA disease and for most patients with stage IIIB. However, patients with tumor burdens which include pelvic disease and B symptoms require a different approach.