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M.V. LOMONOSOV MOSCOW STATE UNIVERSITY
FACULTY OF BASIC MEDICINE
COMPARISON OF POLY- CHEMOTHERAPY (CVD regimen) & THE SAME CHEMOTHERAPY (CT) PLUS INTERFERON-α2a IN METASTATIC
MELANOMAStudent:
Dr. Kyaw Thura Zaw Scientific Supervisor :
Prof. Dr. Lev Demidov
N.N. BLOKHIN CANCER RESEARCH CENTRE
Moscow ,2010
INTRODUCTIONMalignant melanoma is a neoplasm of
melanocytes or 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 of about 6–9 months .
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.
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.
RaceMelanoma is more common in whites than in blacks and Asians. The rate of melanoma in blacks is estimated to be 1/120 that of whites. SexMelanoma 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.
Risk Factors
Sun Exposure and Sun beds Nevi Skin Pigmentation Solar Elastosis and Solar Keratoses Gene Alterations Somatice Alterations Common Low Penetratace Genes
A=Asymmetry B=Border (irregular)
C= Color D= Diameter
ABCD Properties of Radial Melanomas
A 1.5-cm melanoma with characteristic asymmetry, irregular borders, and color variation.
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
AIM OF STUDY
To Study and Compare the Poly-chemotherapy (CVD regimen) & the
Same Chemotherapy(CT)plus Interferon α- 2 a in Metastatic
Melanoma.
Objectives of Study1. To study the response rate of poly
chemotherapy (CVD regimen) and the same chemotherapy (CT) plus interferon-α2a in metastatic melanoma.
2. To study the effect of combine Chemotherapy (CVD) in metastatic melanoma.
3. To study Bio chemotherapy not more rather than Chemotherapy alone.
Materials and Methods
CVD P CVD+IFN P
Age, median (min-max) 55 (35-65) P<0.01 52(30-65) P<0.10
ECOG PS 0 2 P=1.00 2 P=1.00
1 3 P>0.10 6 P>0.25
2 10 P>0.10 7 P>0.30
Metastatic sitesSkin 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
Patient’s Characteristics
Treatment Schedules
• The treatment regimen A consisted of Dacarbazine :800mg/m2 IV day 1, Vinblastine :1.6 mg/m2 IV days 1-5, and Cisplatin : 20 mg/m2 IV days 1-4 (CVD). The cycle was repeated on day 22.
• The treatment regimen B consisted of CVD chemotherapy plus IFN alpha-2a 1.5x106 IU/m2 days 1-10. The total number of cycles/day was 6 at the most.
Response of Therapy
CR: Complete Response, PR: Partial Response ,
SD: Stable Disease
PD: Progressive Disease.
COMPARISON BETWEEN THE RESULT OF CVD AND CVD+IFN
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)
Overall survival. Heavy line represents CVD + IFN group; Fine line represents CVD group;
CONCLUSIONS1. Response rate was the highest best in
CVD+IFN group (6/15)compared to CVD (4/15) , but the difference was not significant.
2. Combined Chemotherapy(CVD) and Biochemotherapy (CVD+IFN) in which, all showed some activity in Metastatic Melanoma.
3. The best responding metastatic sites were the lymph nodes all patients experienced mild adverse effects. No treatment-related deaths occurred. The median survival was 12months in CVD+IFN, CVD respectively.