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Chemotherapy for HD
Complicaitons of chemotherapy for HD
Prognostic Factors
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Pathology & Histologic Subtypes

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)

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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)



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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).

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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.

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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.

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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%

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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.


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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

PATHOLOGICAL BASIS OF HODGKIN'S DISEASE
--RS cells: CD30 & CD15 positive in classical HD (CD15 negative in lymphocyte predominant subtype)
--EBV genome detected in tumor samples (in RS cells?)
--To make the diangosis, sometimes multiple biopsies need to be taken given the presence of many reactive hyperplastic nodes.



HODGKIN'S DISEASE SUBTYPES:

1. NODULAR SCLEROSING
Most common in USA. Usually young female.
--broad birefringent bands of collagen that divide the lymphoid tissue into macroscopic nodule.
--RS variant- the lacunar cell

2. MIXED CELLULARITY
Second most common. Usually young male.
Patients usually present with generalized lymphadenopathy & extranodal disease
--bands of collagen are absent
--cellular background consists of those resembling lymphocytes, eosinophils, PMNs, histiocytes

3. LYMPHOCYTE-PREDOMINANT
Infrequent
Usually localized & is treated with XRT alone. Late relapses are seen
--Few RS cells or variant. Note that they are CD20 POSITIVE & CD15 NEGATIVE. Perhaps this disease is distinct from the rest of the HD subtypes!
--There is background lymphocytes (nodular or diffuse)

4. LYMPHOCYTE-DEPLETION
Rare
Usually presents with advanced stage & extranodal
Usually aggressive with poor prognosis
May be seen in HIV patients, elderly, or more commonly seen in underdeveloped countries!!
--Numerous RS cells
--Cellular background is sparse
--May see diffuse fibrosis or necrosis