1. M.V. LOMONOSOV MOSCOW STATE UNIVERSITYFACULTY OF BASIC MEDICINE COMPARISON OFPOLY- CHEMOTHERAPY (CVD regimen) & THE SAME CHEMOTHERAPY (CT) PLUS INTERFERON-2a IN METASTATIC MELANOMA Student: Dr. Kyaw Thura ZawScientific Supervisor :Prof. Dr. Lev DemidovN.N. BLOKHIN CANCER RESEARCH CENTREMoscow ,2010

2. INTRODUCTION

Malignant melanoma is a neoplasm of melanocytesor of the cells that develop from melanocytes.

Melanoma is showing a rapid worldwide rise in incidence, with a yearly increase of about 5% and a frequent occurrence in young adults . Even though surgery represents the cure in the early phase of disease, the prognosis in patients with metastatic melanoma remains very poor, with a median survival ofabout 69 months .

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Melanoma signaling cascades MAPK and PI3K. The MAPK pathway is hyperactivated in melanomas, mainly due to activating mutations in either the NRAS or BRAF genes .

4. Epidemiology

Frequency: Queensland, Australia, has the highest incidence of melanoma in the world, approximately 57 cases / 100,000 people / year. Israel also has one of the highest incidences,approximately 40 cases / 100,000 people annually.

Incidence: Increasing rapidly worldwide, and faster rate than that of any other cancer except lung cancer in women. Melanoma is notorious for affecting young and middle-aged people.

5. Race Melanoma is more common in whites than in blacks and Asians. The rate of melanoma in blacks is estimated to be1/120that of whites.Sex Melanoma is slightly more common in men than women (1.2:1). Melanoma is the 5th most common malignancy in men and the 6th most common malignancy in women, accounting for 5% and 4% of all new cancer case. respectively. 6. Risk Factors

Sun Exposure and Sun beds

Nevi

Skin Pigmentation

Solar Elastosis and Solar Keratoses

Gene Alterations

Somatice Alterations

Common Low Penetratace Genes

7. A=AsymmetryB=Border (irregular) C= Color D= Diameter ABCD Properties of Radial Melanomas 8. A 1.5-cm melanoma with characteristicasymmetry, irregular borders, and color variation. 9. Factors Predicting the Outcome of Response of Treatment

Good performance status

Soft tissue disease or only a few visceral metastases

Age younger than 65 years

No prior chemotherapy

Normal hepatic and renal function

Normal CBC count

Absence of CNS metastases

10. AIM OF STUDY To Study and Compare thePoly-chemotherapy (CVD regimen) & the Same Chemotherapy(CT)plus Interferon - 2 a in Metastatic Melanoma. 11. Objectivesof Study

To study the response rate of poly chemotherapy (CVD regimen) and the same chemotherapy (CT) plus interferon-2a in metastatic melanoma.

To study the effect of combine Chemotherapy (CVD) in metastatic melanoma.

To study Bio chemotherapy not more rather than Chemotherapy alone.

12. Materials and Methods 13. Patients Characteristics CVD PCVD+IFN P Age , median (min-max) 55 (35-65) P0.25 2 10 P>0.10 7 P>0.30 Metastatic sites Skin 4 P>0.25 6 P>0.10 Lymph node 10 P>0.70 9 P>0.25 Lungs 9 P=1.00 9 P=1.00 Liver 9 P>0.10 6 P>0.10 Other 3 P>0.10 0 P>0.20 Number of Metastases 1 1 P>0.10 4 P>0.10 2 8 P>0.70 7 P>0.70 3 6 P>0.25 4 P>0.25 14. Treatment Schedules

The treatment regimen A consisted ofDacarbazine : 800mg/m2 IV day 1,Vinblastine : 1.6 mg/m2 IV days 1-5, andCisplatin :20 mg/m2 IV days 1-4(CVD) . The cycle was repeated on day 22.

ThetreatmentregimenBconsistedofCVDchemotherapyplus IFN alpha-2a1.5x10 6IU/m2 days 1-10. The total number of cycles/day was 6atthemost .

15. Response of Therapy 16.

CR: Complete Response, PR: Partial Response ,

SD: Stable Disease

PD: Progressive Disease.

COMPARISON BETWEEN THE RESULT OF CVD AND CVD+IFN 17. Overall survival. Heavy line represents CVD + IFN group; Fine line represents CVD group ; No. of death /Total No. Average survival Survival Median CVD+IFN 8/15 13.51(9.7;17.3) 12.0(9.9;14.1) CVD 7/15 10.75(9.1;12.4) 12.0(7.8;16.2) 18. CONCLUSIONS

ResponseratewasthehighestbestinCVD+IFNgroup(6/15)compared to CVD (4/15) , but the difference was not significant.

Combined Chemotherapy(CVD) and Biochemotherapy (CVD+IFN) in which, all showed some activity in Metastatic Melanoma.

The best responding metastatic siteswere the lymph nodes all patients experienced mild adverse effects. No treatment-related deaths occurred. The median survival was 12monthsinCVD+IFN,CVDrespectively.

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