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Chemotherapy for metastatic tumors to the central nervous system

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Abstract

Management of patients with central nervous system metastases poses numerous challenges. This review focuses on the use of chemotherapy in these patients, addressing treatment difficulties such as drug resistance and possible solutions. The impact of the blood-brain barrier is considered less of a limitation than once thought. The advent of targeted signal transduction inhibitors is noted in this context. The current efficacy of chemotherapeutic agents and combinations is also discussed, with results from large studies highlighting a positive survival trend for chemotherapy in selected tumor histologies.

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References and Recommended Reading

  1. Barron KD, Hirano A, Araki S, Terry RD: Experiences with neoplasm involving the spinal cord. Neurology 1958, 9:91–106.

    Google Scholar 

  2. Posner JB, Chernik NL: Intracranial metastases from systemic cancer. Adv Neurol 1978, 19:579–592. This article is a large retrospective analysis of CNS metastases.

    PubMed  CAS  Google Scholar 

  3. Komaki R, Cox JD, Stark R: Frequency of brain metastasis in adenocarcinoma and large cell carcinoma of the lung: correlation with survival. Int J Radiat Oncol Biol Phys 1983, 9:1467–1470.

    PubMed  CAS  Google Scholar 

  4. Fujita A, Fukuoka S, Takabatake H, et al.: Combination chemotherapy of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with brain metastases from non-small cell lung cancer. Oncology 2000, 59:291–295.

    Article  PubMed  CAS  Google Scholar 

  5. Ponta H, Sleeman J, Herrlich P: Tumor metastasis formation: cell-surface proteins confer metastasis-promoting or -suppressing properties. Biochim Biophys Acta 1994, 1198:1–10.

    PubMed  CAS  Google Scholar 

  6. Hall WA, Djalilian HR, Nussbaum ES, Cho KH: Long-term survival with metastatic cancer to the brain. Med Oncol 2000, 17:279–286.

    PubMed  CAS  Google Scholar 

  7. Kaba SE, Kyritsis AP, Hess K, et al.: TPDC-FuHu chemotherapy for the treatment of recurrent metastatic brain tumors. J Clin Oncol 1997, 15:1063–1070. This article represents one of the first large clinical trials for CNS metastasis.

    PubMed  CAS  Google Scholar 

  8. Murray N, Livingston RB, Shepherd FA, et al.: Randomized study of CODE versus alternating CAV/EP for extensive-stage small-cell lung cancer: an Intergroup Study of the National Cancer Institute of Canada Clinical Trials Group and the Southwest Oncology Group. J Clin Oncol 1999, 17:2300–2308.

    PubMed  CAS  Google Scholar 

  9. Postmus PE, Haaxma-Reiche H, Smit EF, et al.: Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy. A phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 2000, 18:3400–3408. This article represents a very large study of single histology that is likely to be a prototype of future studies.

    PubMed  CAS  Google Scholar 

  10. Robinet G, Thomas P, Breton JL, et al.: Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Francais de Pneumo-Cancerologie (GFPC) Protocol 95-L. Ann Oncol 2001, 12:59–67. This study demonstrated in a prospective manner the value of chemotherapy in patients with brain metastasis.

    Article  PubMed  CAS  Google Scholar 

  11. Shepherd FA, Dancey J, Ramlau R, et al.: Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000, 18:2095–2103. This report from a prospective study demonstrates that chemotherapy in this group of patients is more beneficial than supportive care alone.

    PubMed  CAS  Google Scholar 

  12. Sorensen JB, Stenbygaard LE, Dombernowsky P, Hansen HH: Paclitaxel, gemcitabine, and cisplatin in non-resectable non-small-cell lung cancer. Ann Oncol 1999, 10:1043–1049.

    Article  PubMed  CAS  Google Scholar 

  13. Thiebaut F, Tsuruo T, Hamada H, et al.: Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci U S A 1987, 84:7735–7738.

    Article  PubMed  CAS  Google Scholar 

  14. Donelli MG, Zucchetti M, D’Incalci M: Do anticancer agents reach the tumor target in the human brain? Cancer Chemother Pharmacol 1992, 30:251–260. This is a good overview article concerning blood-brain barrier penetration of chemotherapy agents.

    Article  PubMed  CAS  Google Scholar 

  15. Stewart DJ, Leavens M, Maor M, et al.: Human central nervous system distribution of cis-diaminedichloroplatinum and use as radiosensitizer in malignant brain tumors. Cancer Res 1982, 42:2472–2479.

    Google Scholar 

  16. Lesser GJ: Chemotherapy of cerebral metastases from solid tumors. Neurosurg Clin North Am 1996, 7:527–536.

    CAS  Google Scholar 

  17. Twelves CJ, Souhami RL, Harper PG, et al.: The response of cerebral metastases in small cell lung cancer to systemic chemotherapy. Br J Cancer 1990, 61:147–150.

    PubMed  CAS  Google Scholar 

  18. Krisjansen PEG, Sorenson PS, Hansen MS, et al.: Prospective evaluation of the effect on initial brain metastases from small-cell lung cancer of platinum-etoposide based induction chemotherapy followed by an alternating drug regimen. Ann Oncol 1993, 4:579–583. This article represents one of the first large clinical trials for CNS metastasis.

    Google Scholar 

  19. Grossi F, Scolaro T, Tixi L, et al.: The role of systemic chemotherapy in the treatment of brain metastases from small-cell lung cancer. Crit Rev Oncol Hematol 2001, 137:61–67.

    Google Scholar 

  20. Kollmannsberger C, Nichols C, Bamberg M, et al.: First-line high-dose chemotherapy ±radiation therapy in patients with metastatic germ-cell cancer and brain metastases. Ann Oncol 2000, 11:553–559.

    Article  PubMed  CAS  Google Scholar 

  21. Rustin GJ, Newlands ES, Bagshawe KD, et al.: Successful management of metastatic and primary germ cell tumors in the brain. Cancer 1986, 57:2108–2113.

    Article  PubMed  CAS  Google Scholar 

  22. Stewart DJ, Lu K, Benjamin RS, et al.: Concentrations of vinblastine in human intracerebral tumor and other tissues. J Neurooncol 1983, 1:139–144. This article helps to define the role of the blood-brain barrier with respect to CNS tumors.

    PubMed  CAS  Google Scholar 

  23. Postmus PE, Holthuis JJ, Haaxma-Reiche H, et al.: Penetration of VP 16-213 into cerebrospinal fluid after high-dose administration. J Clin Oncol 1984, 2:215–220.

    PubMed  CAS  Google Scholar 

  24. Lloyd BH, Platt-Higgins A, Rudland PS, Barraclough R: Human S100A4 (p9Ka) induces the metastatic phenotype upon benign tumour cells. Oncogene 1998, 17:465–473.

    Article  PubMed  CAS  Google Scholar 

  25. Wu GS, El-Deiry WS: Apoptotic death of tumor cells correlates with chemosensitivity, independent of p53 or bcl-2. Clin Cancer Res 1996, 2:623–633. This article demonstrates the importance of being able to induce apoptosis as a major component of chemotherapy sensitivity of tumor cells.

    PubMed  CAS  Google Scholar 

  26. Mashimo T, Watabe M, Hirota S, et al.: The expression of the KA11 gene, a tumor metastasis suppressor, is directly activated by p53. Proc Natl Acad Sci U S A 1998, 95:11307–11311.

    Article  PubMed  CAS  Google Scholar 

  27. Sun Y, Wicha M, Leopold WR: Regulation of metastasis-related gene expression by p53: a potential clinical implication. Mol Carcinog 1999, 24:25–28.

    Article  PubMed  CAS  Google Scholar 

  28. Roetger A, Merschjann A, Dittmar T, et al.: Selection of potentially metastatic subpopulations expressing c-erB-2 from breast cancer tissue by use of an extravasation model. Am J Pathol 1998, 153:1797–1806. This article is helpful in describing the concept that metastatic subpopulations of cells can be different than the original primary tumor.

    PubMed  CAS  Google Scholar 

  29. Petersen I, Hildalgo A, Petersen S, et al.: Chromosomal imbalances in brain metastases of solid tumors. Brain Pathol 2000, 10:395–401.

    Article  PubMed  CAS  Google Scholar 

  30. Nugent JL, Bunn PA Jr, Matthews MJ, et al.: CNS metastases in small cell bronchogenic carcinoma: increasing frequency and changing pattern with lengthening survival. Cancer 1979, 44:1885–1893.

    Article  PubMed  CAS  Google Scholar 

  31. Gaspar L, Scott S, Rotman M, et al.: Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 1997, 37:745–751. This is the definitive article that designates the prognostic class for patients with metastatic brain tumors.

    Article  PubMed  CAS  Google Scholar 

  32. Postmus PE, Smit EF: Chemotherapy for brain metastases of lung cancer: a review. Ann Oncol 1999, 10:753–759. A very good review of chemotherapy for brain metastases.

    Article  PubMed  CAS  Google Scholar 

  33. Hwu WJ: New approaches in the treatment of metastatic melanoma: thalidomide and temozolomide. Oncology 2000, 14:25–28.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 0431, 77030, Houston, TX, USA

    Charles A. Conrad MD

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  1. Charles A. Conrad MD
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Conrad, C.A. Chemotherapy for metastatic tumors to the central nervous system. Curr Oncol Rep 3, 490–494 (2001). https://doi.org/10.1007/s11912-001-0070-z

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  • DOI: https://doi.org/10.1007/s11912-001-0070-z

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