ABVD Doxorubicin 25 mg/m2 IVB days 1,15 Bleomycin 10 mg/m2 IVB days 1,15 Vinblastine 6 mg/m2 IVB days 1,15 Dacarbazine 375 mg/m2 IVB days 1,15 Repeat cycle every 28 days for 6 cycles Ref: Bonnadonna G, et al: Cancer Clin Trials 2:217 (1979) ------------------------------------------------------------ STANFORD V DOXORUBICIN 25 mg/m2 IV days 1 & 15 VINBLASTINE 6 mg/m2 IV days 1 & 15 MECHLORETHAMINE 6 mg/m2 IV day 1 VINCRISTINE 1.4 mg/m2 (max dose 2 mg) IV days 8 & 22 BLEOMYCIN 5 U/m2 IV days 15 & 16 PREDNISONE 40 mg/m2 PO every other day. Taper by 10 mg every other day starting at week 10. REPEAT CYCLE EVERY 28 DAYS FOR TOTAL OF 3 CYCLES. RADIOTHERAPY TO BE GIVEN TO SITES >5 CM (DOSE 36 CGY) ------------------------------------------------------------ MOPP Mechlorethamine 6 mg/m2 IVB days 1 & 8 Vincristine 1.4 mg/m2 IVB* days 1 & 8 Procarbazine 100 mg/m2 PO days 1-14 Prednisone 40 mg/m2 PO days 1-14 every other cycle** Repeat cycle every 28 days. *No maximum vincristine dose. **Prednisone dose should be tapered. Ref: DeVita VT, et al: Ann Int Med 73:881 (1970). ------------------------------------------------------------ MOPP/ABV Mechlorethamine 6 mg/m2 IV day 1 Vincristine 1.4 mg/m2 IV day 1 Procarbazine 100 mg/m2 PO days 1-7 Prednisone 40 mg/m2 PO days 1-14 Doxorubicin 35 mg/m2 IV day 8 Bleomycin 10 U/m2 IV day 8 Vinblastine 6 mg/m2 IV day 8 Note: Repeat the cycle every 28 days. Each dose of bleomycin is preceded by 100 mg of hydorcortizone IV. If chemical phlebitis occurs from mechlorethamine, 600 mg/m2 of cyclophosphamide may be substituted. Ref: Klimo P, Connors JM; J Clin Oncol 3:1174-1182, 1985. ------------------------------------------------------------
Note: ABVD does not cause leukemia, infertility, or premature menopause & induces less cumulative toxicity (when comapred to MOPP or hybrid regimen). COMPLICATIONS OF CHEMOTHERAPY: 1. MOPP COMPLICATIONS: MDS, AML, rarely ALL. Can happen from 2 yrs up to 10 years after therapy. Chromosomes involved are 5, 7, and 18! Lung cancer & NHL can happen 15 years later. Infertility can occur in 80% with permanent azoospermia or oligospermia if MOPP>3 cycles. With ABVD this risk is at most 15-25%. 2. ABVD COMPLICATIONS: Infertitily minimal. Bleomycin can cause pulmonary complications. 53% will have DOE or cough during therapy. 37% will have decreased pulmonary function. Both FVC and DLCO can decrease follwing ABVD therapy. Cardiomyopathy can occur due to adriamycin if cumulative dose above 400 mg/m2.
_____________________________________________________________ Prognostic Factors: Gender: male Age: >45 Stage: IV Hgb: <105 g/L WBC" >15 X 10e9 Lymphocytes: <0.6 X 10e9 or <8% of WBC diff Serum Albumin: <40 g/L 0-3 factors-------> 5-yr FFP 70% 4-7 factors-------> 5-yr FFP 47%
_____________________________________________________________ Treatment Based on Stage & Risk Factors: STAGE I-II SUBTOTAL LYMPHOID XRT -mantle & para-aortic fields only -patients need to be pathologically staged ie laparotomy. -The 15-20 yr survival rate is 90% & RFS is 75-80% -Most relapses occur within the first 3 years. More than 50% are curable with standard chemotherapy at that time. COMBINED MODALITY THERAPY -If patient has bulky mediastinal disease, B-symptoms, mixed cellullarity or lymphocyte-depletion histology, or age>40. -If not using laparotomy as part of staging procedure, then brief combination chemotherapy followed by XRT is the treatment of choice. -Special Presentations (no laparotomy required): 1. LYMPHOCYTE-PREDOMINANT HD confined to unilateral high neck or epitrochlear lymph node ---> Recommend treatment with XRT only 2. NODULAR SCLEROSING HD non-bulky stage IA in the anterior mediastinum ---> Recommend treatment with XRT only COMBINATION CHEMOTHERAPY -not recommended in early stage disease because it does not increase response compared to XRT. However, if relapses do occur in chemotherapy-treated patient, then response to salvage is poor. STAGE III-IV COMBINATION CHEMOTHERAPY ABVD ABVD alternating with MOPP STANFORD V REGIMEN MOPP --In general, RR higher for ABVD containing regimen vs MOPP alone (83% vs 65%). The reason probably is because ABVD regimen were better tolerated & therefore less dose modifications were needed. COMBINED MODALITY THERAPY Adding low dose XRT to all initial disease sites after chemotherapy-induced CR decreases the relapse rate by 25% & in some studies OS is improved too. However, meta-analysis has shown that even though relapse rate is decreased, overall survival does not change. Perhaps more deaths from other causes in combined modality group. JCO 16:818,1998. _____________________________________________________________ TECHNICAL ASPECTS OF RADIATION THERAPY IN HD: 1. MANTLE FIELD Base of mandible to the diaphragm. Covers LNs above the diaphragm including submandibular, cewrvical, supraclavicular, infraclavicular, axillary, mediastinal, & hilar nodes. 2. PARA-AORTIC FIELD From aortic bifurcation up to the bottom of the mantle field! Spleen and hilar nodes are included. 3. PELVIC FIELD Iliac, inguinal, femoral nodes. Superior border at L5 (bottom of para-aortic field) 4. INVERTED-Y FIELD Para-aortic + pelvic fields 5. TOTAL LYMPHOID IRRADIATION Mantle + Para-aortic + pelvic fields 6. SUBTOTAL LYMPHOID IRRADIATION Mantle + Para-aortic fields DOSE CONSIDERATIONS 1. To each field: 3600 cGy over 4 weeks + boost to involved areas 540-900 cGy. Total 4140-4500 cGy 2. For consolidation following chemotherapy: 2000-3600 cGy in 150-180 cGy fractions 3. If including the liver: Use 50% transmission liver block during the para-aortic field radiation 4. If including the lungs: Place 35% block during mantle field radiation 5. If including the heart: 1500 cGy for cardiac silhouette |