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Aung citt nyein

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    Aung citt nyein Aung citt nyein Presentation Transcript

    • M.V. LOMONOSOV MOSCOW STATE UNIVERSITY FACULTY OF BASIC MEDICINE Complex Combination Biochemotherapy In Advanced Metastatic Melanoma Dr. Aung Citt Nyein (M.B.,B.S) Scientific Supervisor: Prof. Dr. Lev Demidov N.N. BLOKHIN CANCER RESEARCH CENTRE MOSCOW, 2010 N.N. BLOKHIN CANCER RESEARCH CENTRE
    • INTRODUCTION
      • Melanoma is leading cause of death from cutaneous malignancies. According to a WHO report about 160,000 new cases of melanoma were found and 48,000 melanoma related deaths occur worldwide per year.
      • Incidence is highest in the white populations of North America, Europe, and Australia.
      • In United States alone, there were nearly 60,000 new cases of melanoma and more than 8000 melanoma-related deaths in 2007.
      • It is the second most common cancer diagnosis for women and the third most common cancer diagnosis for men.
      • With incidence rates doubling every 10 to 15 years over the past 40 to 50 years, melanoma is an important health problem for countries with populations of European (Caucasian) origin.
    • AIM OF STUDY
      • The aim of this study is to study the benefits
      • and toxicities of complex combination
      • biochemotherapy regimen in advanced metastatic
      • melanoma .
    • RESEARCH OBJECTIVES
      • 1 .To determine the responses of complex combination biochemotherapy .
      • 2 .To determine the severe toxicities of complex combination immunochemotherapy.
      • 3 .To determine dosage reduction for each of the chemo and immunotherapeutics is important in this biochemotherapy regimen.
    • RISK FACTORS
      • Environmental causes of melanoma
        • Exposure to sunlight
        • Ultraviolet radiation exposures
          • Fluorescent lamps
          • Sunlamps or sunbed use
        • Therapeutic Radiation
      • Patient characteristics associated with melanoma
        • Occupational and socioeconomic status
        • Individual history of melanoma
        • Common and atypical naevi
        • Hereditary factors
    • CHARACTERISTICS OF MELANOMA
      • The classic appearance of primary cutaneous
      • melanoma is summarized by the mnemonic ABCD –
        • asymmetry
        • border irregularity
        • color variation
        • diameter greater than 6 mm
    • Superficial Spreading Melanoma
    • Large Nodular Melanoma
    • TREATMENT REGIMENS
      • Single-agent regimens
      • - Dacarbazine : 250 m g / m ² IV on days 1-5. Repeat
      • cycle every 21 days (or)
      • - Dacarbazine : 850 m g / m ² IV on day 1.Repeat cycle
      • every 3-6 weeks.
      • - Interferon α-2b: 20 million IU/m² IM , 3 times weekly
      • for 12 weeks.
      • - Aldesleukin (IL-2): 100,000 IU/kg IV on days 1-5 and 15-
      • 19 .Repeat cycle every 28 days.
      • - Temozolomide: 150 m g / m ² PO on days 1-5. Repeat
      • cycle every 28 days. If well tolerated, can increase
      • dose to 200 m g / m ² PO on days 1-5.
      • Combination regimens
      • DTIC + BCNU + Cisplatin
      • Dacarbazine: 220 m g / m ² IV on days 1-3
      • Carmustine: 150 m g / m ² IV on day 1
      • Cisplatin: 25 m g / m ² IV on days 1-3
      • Repeat cycle with dacarbazine and cisplatin every 21 days
      • and carmustine every 42 days .
      •   IFN + DTIC
      • Interferon α-2b: 15 million IU/m² IV on days 1-5, 8 - 1 2 ,
      • and 1 5 - 1 9 as induction therapy .
      • Interferon α-2b: 10 million IU/m² SC 3 times weekly after
      • induction therapy .
      • Dacarbazine: 200 m g / m ² IV on days 2 2 - 2 6 .Repeat
      • cycle every 28 days.
      • Temozolomide + Thalidomide
      • Temozolomide: 75 mg/m² /day PO for 6 weeks .
      • Thalidomide: 2 0 0 - 4 0 0 mg/m² /day PO for 6
      • weeks . Repeat cycle every 10 weeks.
      • Adjuvant therapy
      • Interferon α -2b
      • Interferon α-2b: 20 million IU/m² IV, 5 times
      • weekly for 4 weeks, then 10 million IU/m² SC,
      • 3 times weekly for 48 weeks . Treat for total of
      • one year.
    • Material and Methods
      • Total Number ( n ) = 25
      • Therapeutic Regimen
      Regimen Treatment Schedule DTIC 850 mg / m² iv , day 1 Vindesine 1.6 mg / m² iv , days 1-5 Cisplatin 20 mg / m² iv , days 2-5 Interleukin-2 9 MU / m² iv , days 1-5 Interferon- α 2b 5 MU IE sc , days 1-5
    • Patients Characteristics (No. of organ affected)
    • Patients Characteristics (Previous Therapy)
    • Tumour response to therapy CR -complete remission : PR -partial remission : SD -stable disease : PD -disease progression
    • Toxicities of Chemo and Immunotherapeutic Agents Toxic Effects
    • Dosage reduction for each of the chemo and Immunotherapeutics Agents Reduction Rate
    • CONCLUSION
      • 1. High response rates were observed by combining
      • chemotherapy and immunotherapy. In our patients
      • complete remission was verified in 2 patients ,
      • partial remission was in 2 patients and stable
      • disease was in 9 patients. Five of 25 patients had
      • disease progression. Although a majority of
      • responses was stable diseases (36%), an objective
      • response rate of 16% was observed with a CR rate
      • of 8% in our patients.
      • 2. Lethargy, fever, nausea and vomiting were observed in most of the patients. Thrombocytopenia was observed in 10 patients, leukopenia was in 9 patients, neutropenia was in 5 and anaemia was in 4 patients respectively. In our patients haematoloigcal toxicities were mostly observed and they are major side effects for our patients.
      • 3. Doses of vindesine and cisplatin were mostly reduced due to toxicities , totally in 15 and 12 patients respectively. Regarding the immunotherapy, because of severe hypotension and oedema in the context with the capillary leak syndrome a dose reduction of IL-2 was necessary. So, in this regimen dosage reduction was need due to severe toxicities of therapeutic agents.
    •