Treatment of MOPP-resistant Hodgkin's disease with adriamycin,bleomycin, vinblastine and dacarbazine (ABVD)

ABVD chemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) was given in monthly courses to 20 patients with Hodgkin's disease resistant to MOPP. Complete responses were achieved in 10 of the 18 evaluable patients (55%). Responses occurred rapidly with a median of 3 months. Nine of the 10 complete responders are presently off all therapy and remain disease-free after 9–60 months. The actuarial median survival for all patients is 38 months. Toxicity caused by ABVD was acceptable. ABVD is a useful salvage chemotherapy program for patients with Hodgkin's disease resistant to MOPP.     

Prolonged disease-free survival in MOPP-resistant Hodgkin's disease after treatment with adriamycin,bleomycin, vinblastine and dacarbazine (ABVD)

Summary Twenty-one patients with advanced Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, prednisone) were treated with ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). ABVD induced complete remission in 13 patients (62%) and partial remission in 2 (9.5%). In particular, complete response to ABVD was obtained in 7 of 13 patients who failed to respond to primary MOPP chemotherapy. After six cycles, no further therapy was given to patients in complete remission. At 36 months from starting ABVD, 69.7% of complete responders remain alive and free of disease, with a total survival of 73.4%. In contrast, none of the patients in whom partial response or nonresponse was observed was alive at 18 months. ABVD for six cycles was accompanied by mild and reversible toxicity. The results indicate that there is no cross-resistance between MOPP and ABVD. ABVD appears a simple, effective, and tolerable multiple-drug chemotherapy for use in patients who are resistant to MOPP.     

Combination chemotherapy of Hodgkin's disease with adriamycin, bleomycin, vinblastine, and imidazole carboxamide versus MOPP.

This paper reports the preliminary results of a controlled study randomizing MOPP vs. a new four-drug combination (ABVD) in advanced Hodgkin's disease. ABVD consists of 6 cycles of adriamycin, bleomycin, vinblastine, and imidazole carboxamide. The purpose for designing this new combination was two-fold: to compare the efficacy of ABVD with MOPP, and to demonstrate absence of cross-resistance between the two regimens. Of 60 patients entered into the study, 45 (MOPP25, ABVD20) are presently evaluable for the analysis of remission induction. No patient was previously treated with chemotherapy; 20% had relapsed after primary radiotherapy. Whenever possible, complete remission was defined also through rebiopsy of known organ involvement. Complete remission occurred in 76% of patients treated with MOPP and in 75% of those given ABVD, with no difference between the two regimens as far as stage (IIIB-IIIS and IV), histologic type, and prior irradiation were concerned. Crossover carried out for progressive disease or for relapse after initial remission showed absence of cross-resistance between MOPP and ABVD. Toxic manifestations after ABVD were in general well tolerated and reversible. The percent of optimal dose for each drug was as follows: adriamycin 87%, vinblastine 87%, bleomycin 96%, and imidazole carboxamide 96%. These preliminary results indicate that in terms of complete remission, ABVD could represent a successful alternative to MOPP to be used either in MOPP failures or in sequential combination with MOPP. However, the lack of long-term followup limits at the present time an adequate comparison between the two treatments.     

Treatment of MOPP-refractory Hodgkin's disease with vinblastine, doxorubicin, bleomycin, CCNU, and dacarbazine

Eighteen patients with advanced Hodgkin's disease, refractory to combination chemotherapy with nitrogen mustard, vincristine, prednisone, and procarbazine (MOPP), were treated with vinblastine, doxorubicin (Adriamycin), bleomycin, CCNU, and dacarbazine (DTIC) (VABCD). Fifteen patients had Stage IV disease and 11 had systemic symptoms. Although hematologic toxicity was considerable, there was no drug related mortality. Eight patients achieved a complete remission (CR), and five are currently in a continuous CR of five, 24, 30, 34, and 36 months duration, respectively. An additional patient had a 30-month CR and relapsed with localized lymphadenopathy and is currently disease-free following involved-field radiotherapy 46 months from initiation of VABCD. This study suggests that long-term disease-free survival and potential cure can be achieved with VABCD in MOPP-refractory Hodgkin's disease.     

Adriamycin, bleomycin, DIC, CCNU, and prednisone (ABDIC) chemotherapy in MOPP-resistant Hodgkin's disease

ABDIC was administered to 32 patients with MOPP-resistant Hodgkin's disease. Three were considered nonevaluable because of early death. All patients had received MOPP (medium of eight cycles), and five had also received other chemotherapy. Major radiotherapy had been used in 18 of the 29. Complete remission (CR) occurred in 10 of 29 (34.5%), partial remissions (PR) in 14 (48.2%), and no remissions (NR) in five (17.2%). Median survival and relapse-free survival for CR patients exceeded 28 months. Two relapsed at 8 and 18 months; one died at 9 1/2 months, and the other is disease-free with other treatment at 35 months. Seven of the remaining eight patients are alive without disease (10-35 months); 4 are on maintenance therapy, and the other died from an infection and eosinophilic granuloma of lung without evidence of recurrent Hodgkin's disease. Median survival of PR patients was eight months. One patient with Hodgkin's disease involving the liver is alive at 36 months with further therapy. Median survival of NR patients is 2.5 months, and all died within seven months. Survival of CR patients is greater than PR and NR patients (P = 0.002), and that of PR is greater than NR (P = 0.01). Four of the 29 patients had nodal relapse, and 25 had parenchymal relapse, with no difference in response rates (P = 0.47). ABDIC is useful in Hodgkin's disease patients who have had extensive prior chemotherapy and radiotherapy.     

Neutropenia and febrile neutropenia in patients with Hodgkin's lymphoma treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy

When uncomplicated neutropenia during doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy for the treatment of Hodgkin's lymphoma is encountered, it is unclear whether or not treatment should be modified. In the present study, we determined the incidence of neutropenia, febrile neutropenia, and the relationship of febrile neutropenia to grade III/IV neutropenia and dose modification, in a large university patient population. We reviewed the charts of patients diagnosed with Hodgkin's lymphoma between 1 January 1990 and 31 December 2002 who were treated with ABVD chemotherapy, and seen at the University of Iowa with complete diagnosis, staging, and treatment dosing records. Adequate data was available on 894 treatments in 81 patients with Hodgkin's lymphoma treated with ABVD chemotherapy. Grade III/IV neutropenia was present on the scheduled day of treatment in 187 (20.9%) treatments in 64 (79%) patients. Grade III/IV neutropenia was most common at cycle 1 day 15. Febrile neutropenia developed nine times in eight patients, and eight episodes of febrile neutropenia developed when the treatment-day absolute neutrophil count (ANC) > or =1000. Dose delay of >4 days and/or dose reduction to <80% of original doxorubicin dose following grade III/IV neutropenia occurred in 29 of 187 treatments, with no episodes of febrile neutropenia. With grade III/IV neutropenia on the day of therapy, 158 treatments were administered without dose reduction or dose delay with one subsequent episode of febrile neutropenia. Neutropenia during ABVD is common, and dose modification for uncomplicated neutropenia on the day of treatment may not reduce the risk of febrile neutropenia. It may be possible to maintain dose intensity in the face of uncomplicated neutropenia during ABVD therapy.     

Combination chemotherapy of refractory lymphoma with cis-dichlorodiamineplatinum, vinblastine, and bleomycin

Therapy of advanced lymphomas after failure of chemotherapy with cytoxan and adriamycin containing combinations remains poor. We have treated 17 patients with refractory lymphomas of various histologies with an intensive regimen of cisplatin, vinblastine and bleomycin. These were three complete clinical responses (6, 10+, 8 months, respectively) and five partial responses (2.5, 3, 4, 7, 18 months, respectively) for a total of 8/17 responders. Four of the eight responders had bone or bone marrow involvement. In addition, three patients had dramatic shrinkage of measureable lesions, but the duration (less than 1 month) was too short to allow classification as a response. Toxicity included severe myelosuppression requiring that patients be hospitalized to the majority of cases, mild to moderate rise in serum creatinine levels in 41% of patients and one case of fatal pulmonary fibrosis. This regimen may be useful in patients with refractory or relapsing lymphoma; alternatively, it may be useful as part of an initial treatment protocol utilizing non-cross-resistant regimens for the management of patients with poor prognosis lymphomas.     

Long-term follow-up with ABDIC salvage chemotherapy of MOPP-resistant Hodgkin's disease

Thirty-six consecutive patients with advanced recurrent Hodgkin's disease resistant to chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) were treated with doxorubicin (Adriamycin), bleomycin, (dacarbazine) DTIC, (lomustine) CCNU, and prednisone (ABDIC). Among the 34 patients evaluable for response, complete remission occurred in 35% and partial remission in 35%. The achievement of complete remission during primary MOPP induction was a statistically significant prognostic factor that predicted complete remission with ABDIC (p less than 0.01). The median time to complete remission was 2 months (range 1-11 mo). The median relapse-free survival time for complete responders is 47 months, and an estimated 53% of all patients who achieve complete remission are projected to be alive, free of disease off therapy at 3 years from initiation of ABDIC. The median survival of all patients is 24 months. The median survival of complete responders, partial responders, and nonresponders is 70, 17, and 4 months, respectively. The survival curve for complete responders is significantly different from that for partial responders (p less than 0.01); the survival curve for partial responders is also significantly different from that of nonresponders (p less than 0.01). Toxicity of ABDIC was acceptable; only one patient died from complications of myelosuppression. Our results indicate that ABDIC is a potentially curative regimen for a fraction of patients with MOPP-resistant Hodgkin's disease who achieve complete remission with prior MOPP therapy. It also prolongs the survival of patients who do not achieve complete remission with prior MOPP therapy.     

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.     

Consolidation radiation after complete remission in Hodgkin's disease following six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy: is there a need?

PURPOSE: Combined modality treatment using multidrug chemotherapy (CTh) and radiotherapy (RT) is currently considered the standard of care in early stage Hodgkin's disease. Its role in advanced stages, however, continues to be debated. This study was aimed at evaluating the role of consolidation radiation in patients achieving a complete remission after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy using event-free survival (EFS) and overall survival (OS) as primary end points. PATIENTS AND METHODS: Two hundred and fifty-one patients with Hodgkin's disease attending the lymphoma clinic at the Tata Memorial Hospital (Mumbai, India) from 1993 to 1996 received induction chemotherapy with six cycles of ABVD after initial staging evaluation. A total of 179 of 251 patients (71%) achieved a complete remission after six cycles of ABVD chemotherapy and constituted the randomized population. Patients were randomly assigned to receive either consolidation radiation or no further therapy. RESULTS: With a median follow-up of 63 months, the 8-year EFS and OS in the CTh-alone arm were 76% and 89%, respectively, as compared with 88% and 100% in the CTh+RT arm (P =.01; P =.002). Addition of RT improved EFS and OS in patients with age < 15 years (P =.02; P =.04), B symptoms (P =.03; P =.006), advanced stage (P =.03; P =.006), and bulky disease (P =.04; P =.19). CONCLUSION: Our study suggests that the addition of consolidation radiation helps improve the EFS and OS in patients achieving a complete remission after six cycles of ABVD chemotherapy, particularly in the younger age group and in patients with B symptoms and bulky and advanced disease.     

Combination chemotherapy with vinblastine, bleomycin and methotrexate in DTIC-resistant metastatic melanoma.

Fifteen patients with metastatic DTIC-resistant malignant melanoma were treated with vinblastine, bleomycin and methotrexate combination chemotherapy. Three patients showed an objective response (one complete response). The therapy was well tolerated and easy to administer. This combination appears to produce in DTIC-resistance patients a response rate similar to that obtained with DTIC.     

Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). The Lymphoma Study Group of the Japan Clinical Oncology Group

BACKGROUND: The main form of cytotoxic treatment for advanced Hodgkin's disease (HD) is conventional dose multiagents chemotherapy. As HD is not common in Japan, we conducted a phase II study of the commonly used combination chemotherapy (CCT) regimen established in the West for Japanese patients with advanced HD to confirm the efficacy and safety. METHOD: Between October 1989 and February 1993, a multicenter phase II study of alternating CCT C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, vinblastine, bleomycin, dacarbazine) to evaluate its clinical usefulness for clinical stage (cS) II-IV HD was conducted by the Lymphoma Study Group of the Japan Clinical Oncology Group. RESULTS: Seventy-nine previously untreated patients were enrolled in the study. For 67 eligible patients, the response rate was 92.5% with 83.6% complete response (CR). For 40 cS II and 27 cS III/IV patients the response rate was 95.0% with 90.0% CR and 88.9% with 74.1% CR, respectively. The overall 5-year survival rate was 84.8%. Those of cS II and cS III/IV were 92.5 and 73.1%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.1025). The progression-free 4-year survival rate was 72.8%. Those of cS II and cS III/IV were 77.5 and 65.7%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.2483). Grade 4 toxicity by the criteria of the World Health Organization consisted of leukocytopenia in 28.4% of patients. There was GPT elevation in 4.5%, nausea/vomiting in 11.9% and CNS in 1.5% of patients, but there was no treatment-related death. CONCLUSION: The C-MOPP/ABVd regimen for Japanese patients with advanced HD is considered to be one of the effective CCTs according to the results of the present phase II study.     

Hodgkin's disease in HIV-infected patients: report of eight cases usefully treated with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus granulocyte colony- stimulating factor.

In the era prior to active antiretroviral therapy (HAART) andin the absence of growth factors, the response rates of HIV-infectedpeople with Hodgkin’s disease (HD-HIV) with standard chemotherapyranged between 45% and 70%. Median survival was only in theapproximate range of 8–18 months. The underlying complicationsof HIV infection and the unfavourable clinical and biologicalcharacteristics are the major factors affecting survival ofthese patients [1]. The use of granulocyte colony-stimulatingfactor (G-CSF) concomitantly with standard ABVD (doxorubicin,bleomycin, vinblastine, dacarbazine) but without antiretroviraltherapy failed to improve results     

Combination cisplatin, vinblastine, and bleomycin chemotherapy (PVB) for malignant germ-cell tumors of the ovary

Nine women with germ-cell tumors of the ovary (three endodermal sinus tumors, four immature teratomas, and two mixed germ-cell tumors) were treated with cisplatin, vinblastine, and bleomycin (PVB) chemotherapy after cytoreductive operations. Five patients were stage I, three were stage III, and one patient had recurrent disease. All nine women are alive and without evidence of disease with a median follow-up of 31 months from diagnosis and 27 months since completion of PVB. Treatment toxicity although occasionally severe was rapidly reversible.     

Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP).

Twenty-three patients with diffuse histiocytic lymphoma who had not had prior chemotherapy were treated with CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone). Sixteen of these patients had previously been treated with radiation therapy. Nine of these 23 patients had a pathologically documented complete response at the conclusion of CHOP with an overall complete response rate of 39%. In patients whose disease was confined to lymph nodes, the complete response rate was 7 of 8 or 88%, while in patients with stage IV disease, only 2 of 15 or 13% had complete responses. Although prior radiation therapy could not be demonstrated to be an adverse prognostic factor in this small series, it could have accounted for the low overall complete response rate noted. Complete response in this series was well sustained with an actuarial relapse-free survival of 75% and an actuarial survival of 89% at two years. No complete responses occurred in five patients who had received prior chemotherapy.     

Combination chemotherapy with vinblastine, bleomycin, and cis-diamminedichloroplatinum (II) in squamous cell carcinoma of the head and neck

Forty-five patients with advanced squamous cell carcinoma of the head and neck, 23 of whom had received no prior therapy, were given the combination of vinblastine, 4 mg/m2 intravenously (IV) on Day 1; bleomycin, 15 mg/day intramuscularly on Days 1-7; and cis-diamminedichloroplatinum (II), 60 mg/m2 with mannitol diuresis on Day 8. The regimen was repeated at three-week intervals, for a maximum of three cycles. Among the 23 patients without prior surgery or radiation, there were 5 complete responses and 12 partial responses, a 74% response rate; whereas, among the 22 with prior therapy, there were 2 complete responses and 8 partial responses, a response rate of 45%. Nineteen of 23 previously untreated patients were subsequently given radiation, 1 had surgery, and 1 had surgery plus radiation. Twelve of these 19 patients are currently free of disease, with a median duration of ten months from initial response. Four of the 22 previously treated patients received radiation and 2, surgery; 4 of these 6 patients are without evidence of disease. Renal dysfunction with elevation of serum creatinine occurred in 5 patients, a leukocyte count of less than 3,000/mm3 in 3, a platelet count of less than 100,000/mm3 in 2, skin changes in 11, hearing loss in 1, and both peripheral neuropathy and pulmonary changes in 1 patient. This combination of agents has substantial activity in untreated patients and may be useful as initial therapy in advanced head and neck malignancies by diminishing the incidence of local recurrence and distant metastasis.     

Severe vascular toxicity associated with vinblastine,bleomycin, and cisplatin chemotherapy

Summary Vascular toxicity following the use of vinblastine, bleomycin, and cisplatin (VBP) combination chemotherapy has been described. This report gives details of 5 patients who suffered acute life-threatening vascular events following such a chemotherapy regimen for germ cell tumors. In 3 of the cases no evidence of tumor was found at autopsy. Both an acute and a long-term vascular toxicity were seen. Large artery vascular disease may result from synergistic toxicity of the drugs comprising the regimen. These cases, with an additional 16 collected from the literature, suggest that major vascular disease is a significant side-effect of the VBP regimen.Supported by the Jazz and Blues Fund and by the Deborah Goldfine Reva Smilgoff Memorial Fund. Brian Samuels is the Triangle Industries Cancer Research Fellow