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A. Epidemiology

  1. About XXX cases per year
  2. ~80% of patients are male
  3. Strongly associated with asbestos exposure (navy shipyards, construction)
  4. Smoking in persons with asbestos exposure greatly increases risk
  5. Association reported with simian virus 40 (SV40) DNA [40] is likely an artificact [6,55]

B. Pathology

  1. Tumor of mesothelium lining lungs
  2. Not truly a lung parenchymal cancer

C. Presentation

  1. Pleural effusion with breathlessness, often with chest-wall pain (~60% of cases)
  2. Weight loss and fatigue usually occur later in progression (<30% at presentation)
  3. Ascites, abdominal pain are most common in peritoneal malignant mesothelioma
  4. Mesotheliomas can also occur in the pericardium and tunica vaginalis

D. Screening

  1. Chest radiography and/or CT scan in persons at high risk may be warranted
  2. Serum osteopontin level elevation can distinguish persons with exposure to asbestos who do and who do not have pleural mesothelioma [4]
  3. Serum levels of mesothelin and related proteins (SMR) detect early stage mesothelioma [5]

E. Diagnosis

  1. Diagnosis usually from pleural biopsy or analysis of cells in pleural effusion
  2. Positive calretinin and epithelial membrane antigen staining in cytological samples
  3. Must distinguish from lung adenocarcinoma by absence of CEA, CD15, TTF-1, B72.3
  4. Large numbers of non-malignant mesothelial cells may be present in pleural effusions [2]

F. Treatment

  1. Symptomatic Treatment
    1. Glucocorticoids
    2. Analgesic drugs
    3. Bronchodilators
    4. Palliative radiotherapy
  2. Chemotherapy
    1. Standard of care is cisplatin (Platinol®) + pemetrexed (Alimta®) [6]
    2. Phase III comparison of cisplatin ± pemetrexed showed combination had 3 months survival advantage and a 41% response rate [7]
    3. Mitomycin 6 mg/m2, vinblastine 6 mg/m2, cisplatin 50 mg/m2 (MVP) every 3 weeks also used
    4. Alternative is vinorelbine injection 30 mg/m2 weekly x 12 weeks
    5. MVP chemotherapy may not improve quality of life when added to sympatomic treatment [8]
    6. Gemcitabine (Gemzar®) has some activity and improves quality of life
  3. Median survival is ~12 months from diagnosis

G. Pemetrexed (Alimta®) [6]

  1. Antimetabolite inhibits several enzymes involved in folate metabolism:
    1. Dihydrofolate reductase
    2. Thymidylate synthase
    3. Glycinamide ribonucleotide formyltransferase
  2. FDA approved for combination with cisplatin (Platinol®) in malignant pleural mesothelioma
    1. Median survival of combination 12.1 months versus 9.3 months with cisplatin alone
    2. Response rate single agent pemetrexed 14% with 10.7 month median survival
  3. Toxicities
    1. Myelosuppression
    2. Rash
    3. Fatigue
    4. Mouth sores
    5. Nausea and diarrhea
  4. Vitamin B12 1000µg IM q9 weeks and folic acid 350-1000µg po qd reduce toxicities
  5. Dexamethasone 4mg bid x 3 days is begun the day before treatment to reduce rash
  6. Being evaluated in other solid tumor malignancies
  7. Dose is 500mg/m2 IV over 10 minutes q3 weeks
    1. Do not use in patients with creatinine clearance <45mL/min
    2. Do not use with drugs that reduce renal function

References

  1. Robinson BWS, Musk AW, Lake RA. 2005. Lancet. 366(9483):397 abstract
  2. Cornia PB, Lipsky BA, Dhaliwal G, Saint S. 2004. NEJM. 350(14):1443 (Case Discussion) abstract
  3. Robinson BWS and Lake RA. 2005. NEJM. 353(15):1591 abstract
  4. Pass HI, Lott D, Lonardo F, et al. 2005. NEJM. 355(15):1564
  5. Robinson BWS, Creaney J, Lake R, et al. 2003. Lancet. 362(9396):1612 abstract
  6. Pemetrexed. 2004. Med Let. 46(1180):31 abstract
  7. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. 2003. J Clin Oncol. 21:2636 abstract
  8. Muers MF, Stephens RJ, Fisher P et al. 2008. Lancet. 371:(9625)1685 abstract