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M.V. LOMONOSOV MOSCOW STATE UNIVERSITYFACULTY 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 FACTORSEnvironmental causes of melanoma
Exposure to sunlight Ultraviolet radiation exposures
• Fluorescent lamps• Sunlamps or sunbed use
Therapeutic RadiationPatient 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-α2b 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.