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.