Small Cell Lung Cancer Medication

  • Author: Winston W Tan, MD; Chief Editor: Jules E Harris, MD   more...
 
Updated: Mar 1, 2012
 

Medication Summary

The goals of pharmacotherapy are to induce remission, reduce morbidity, and prevent complications.

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Antiemetic agents

Class Summary

Vomiting induced by antineoplastic agents is stimulated through the chemoreceptor trigger zone (CTZ), which then stimulates the vomiting center (VC) in the brain. Increased activity of central neurotransmitters, dopamine in CTZ or acetylcholine in VC, appears to be a major mediator in inducing vomiting. Following administration of antineoplastic agents, serotonin (5-HT) is released from enterochromaffin cells in the gastrointestinal (GI) tract. With serotonin (5-HT) release and subsequent binding to 5-HT3 receptors, vagal neurons are stimulated and transmit signals to the VC, resulting in nausea and vomiting.

Antineoplastic agents may cause nausea and vomiting so intolerable that some patients refuse further treatment. Some antineoplastic agents are more emetogenic than others. Prophylaxis with antiemetic agents before and following cancer treatment is often essential to ensure administration of the entire chemotherapy regimen.

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Metoclopramide (Clopra, Reglan, Maxolon, Octamide PFS)

 

Metoclopramide is a dopamine antagonist that stimulates acetylcholine release in myenteric plexus by acting centrally on the chemoreceptor triggers in the floor of the fourth ventricle, which provides important antiemetic activity.

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Dexamethasone (Decadron)

 

Dexamethasone is a synthetic adrenocortical steroid with multiple indications. This agent is widely used in combination with 5-HT receptor antagonists to prevent nausea and vomiting caused by highly emetogenic agents (eg, cisplatin).

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Ondansetron (Zofran)

 

Ondansetron is a selective 5-HT3-receptor antagonist that is used to prevent chemotherapy-induced nausea and vomiting. It is unclear whether the effect of this agent is centrally and/or peripherally mediated.

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Granisetron (Kytril)

 

Granisetron is a selective 5-HT3-receptor antagonist that is used to prevent chemotherapy-induced nausea and vomiting. Like ondansetron, it is unclear whether the effect of granisetron is centrally and/or peripherally mediated.

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Dolasetron (Anzemet)

 

Dolasetron binds to 5-HT3 receptors located on vagal neurons in the GI tract, blocking signals to the vomiting center, thus preventing nausea and vomiting.

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Palonosetron (Aloxi)

 

Palonosetron is a selective 5-HT3 receptor antagonist with long half-life (40 h) that blocks 5-HT3 receptors peripherally and centrally in the chemoreceptor trigger zone. This agent is indicated for the prevention and treatment of chemotherapy-induced nausea and vomiting.

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Antineoplastic agents

Class Summary

Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (ie, cell-cycle phase G1), followed by DNA synthesis (ie, phase S). The next phase is a premitotic phase (ie, G2); then, finally, mitotic cell division (ie, phase M) occurs.

The cell division rate varies for different tumors. Most common cancers grow very slowly compared with the growth rate of normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover more quickly from chemotherapy than malignant ones, which is the rationale behind current cyclic dosage schedules. Dosage cycles are determined by cancer stage and tolerance of adverse effects.

Antineoplastic agents are used in the curative therapy of limited-stage small cell lung cancer (SCLC) or to prolong survival in extensive-stage disease. These agents interfere with cell reproduction. Some agents are cell-cycle specific, whereas others (eg, alkylating agents, anthracycline, cisplatin) are not. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism of action of many antineoplastic agents.

A phase II study of amrubicin, a synthetic anthracycline drug, showed a response rate of 44% in patients treated with this drug in the second-line setting.[42] Further studies are needed to evaluate its true efficacy in the phase III setting.

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Etoposide (Toposar, VePesid)

 

Etoposide inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in the late S or early G2 portion of the cell cycle.

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Cyclophosphamide (Cytoxan, Neosar)

 

Cyclophosphamide is chemically related to the nitrogen mustards. As an alkylating agent, the mechanism of action of its active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells. Fatal cardiotoxicity has been reported with coadministration of pentostatin.

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Doxorubicin (Adriamycin, Rubex)

 

Doxorubicin inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA. The combination of these 2 events can in turn inhibit the growth of neoplastic cells.

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Vincristine (Oncovin)

 

Vincristine inhibits tubulin polymerization during mitosis. This agent is G2-phase specific. Vincristine may interact with mitomycin-C and cause an acute pulmonary reaction.

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Topotecan (Hycamtin)

 

Topotecan inhibits topoisomerase I and thereby inhibits DNA replication. This agent may interact with other antineoplastic drugs to cause prolonged neutropenia and thrombocytopenia in addition to increasing morbidity/mortality.

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Paclitaxel (Taxol)

 

The mechanisms of action of paclitaxel are tubulin polymerization and microtubule stabilization. This agent may interact with cisplatin to further increase myelosuppression.

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Carboplatin (Paraplatin)

 

Carboplatin is an analogue of cisplatin (ie, platinum-salt alkylating agent) with a similar efficacy but lower toxicity profile. The mechanism of action for cisplatin and carboplatin is the production of cross-links within and between strands of DNA. Carboplatin may interact with aminoglycosides and other nephrotoxic drugs to increase nephrotoxicity and ototoxicity.

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Cisplatin (Platinol)

 

Cisplatin is an alkylating agent that causes intrastrand and interstrand cross-linking of DNA, leading to strand breakage. This agent has a broad range of antitumor activity and is used in testicular, ovarian, and transitional cell carcinomas. Cisplatin forms the backbone of currently available approved combination chemotherapy regimens for non–small-cell lung cancers (NSCLCs) and SCLCs. Administer adequate hydration before and for 24 hours after cisplatin dosing to reduce the risk of nephrotoxicity.

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Docetaxel (Taxotere)

 

Docetaxel is a semisynthetic taxane, a class of drugs that inhibits cancer cell growth by promoting assembly and blocking disassembly of microtubules, thereby preventing cancer cell division, leading to cell death.

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Irinotecan

 

Irinotecan is a derivative of camptothecins and it inhibits topoisomerase I, inhibiting DNA replication, which causes cell death.

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Ifosfamide (Ifex)

 

Ifosfamide is a nitrogen mustard that inhibits DNA and protein synthesis and, thus, cell-proliferation by causing DNA cross-linking and denaturation of double helix.

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Gemcitabine (Gemzar)

 

Gemcitabine is a pyrimidine analog. After intracellular metabolism to active nucleotide, it inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. It is cell-cycle specific for S phase.

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Vinorelbine (Navelbine)

 

Vinorelbine is a vinca alkaloid that inhibits tubulin polymerization during G2 phase of cell division, thereby inhibiting mitosis.

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Contributor Information and Disclosures
Author

Winston W Tan, MD  Assistant Professor of Medicine, Mayo Medical School; Consulting Staff, Mayo Group Practices

Winston W Tan, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Philippine Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Irfan Maghfoor, MD  Consulting Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia

Irfan Maghfoor, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Michael Perry, MD, MS, MACP  Nellie B Smith Chair of Oncology Emeritus, Director, Division of Hematology and Medical Oncology, Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

Michael Perry, MD, MS, MACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, International Association for the Study of Lung Cancer, and Missouri State Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

References

  1. Boffetta P, Trichopoulos D. Cancer of the lung, larynx, and pleura. In: Adami H, Hunter D, Trichopoulos D, eds. Textbook of Cancer Epidemiology. 2nd ed. New York, NY: Oxford University Press; 2008:349-67.

  2. Krug LM, Kris MG, Rosenzweig K, Travis WD. Cancer of the lung. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles & Practice of Oncology. 8th ed. Philadelphia, Pa: Lippincott Williams Wilkins; 2008:947-66.

  3. Tsao A, Glisson B. Small cell lung cancer. In: Kantarjian H, Wolff R, Koller C, eds. MD Anderson Manual of Medical Oncology. New York, NY: McGraw-Hill; 2006:233-56.

  4. Schreiber D, Rineer J, Vongtama D, et al. Surgery for limited-stage small cell lung cancer, should the paradigm shift? A SEER-based analysis. J Clin Oncol (Suppl). 2008;26:403s.

  5. Johnson BE, Ihde DC, Makuch RW, Gazdar AF, Carney DN, Oie H, et al. myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course. J Clin Invest. Jun 1987;79(6):1629-34. [Medline]. [Full Text].

  6. Little CD, Nau MM, Carney DN, Gazdar AF, Minna JD. Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature. Nov 10-16 1983;306(5939):194-6. [Medline].

  7. Schneider PM, Hung MC, Chiocca SM, Manning J, Zhao XY, Fang K, et al. Differential expression of the c-erbB-2 gene in human small cell and non-small cell lung cancer. Cancer Res. Sep 15 1989;49(18):4968-71. [Medline].

  8. Hensel CH, Hsieh CL, Gazdar AF, Johnson BE, Sakaguchi AY, Naylor SL, et al. Altered structure and expression of the human retinoblastoma susceptibility gene in small cell lung cancer. Cancer Res. May 15 1990;50(10):3067-72. [Medline].

  9. Naylor SL, Johnson BE, Minna JD, Sakaguchi AY. Loss of heterozygosity of chromosome 3p markers in small-cell lung cancer. Nature. Oct 1-7 1987;329(6138):451-4. [Medline].

  10. D'Amico D, Carbone D, Mitsudomi T, Nau M, Fedorko J, Russell E, et al. High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. Oncogene. Feb 1992;7(2):339-46. [Medline].

  11. Mitsudomi T, Lam S, Shirakusa T, Gazdar AF. Detection and sequencing of p53 gene mutations in bronchial biopsy samples in patients with lung cancer. Chest. Aug 1993;104(2):362-5. [Medline].

  12. WYNDER EL, GRAHAM EA. Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma; a study of 684 proved cases. J Am Med Assoc. May 27 1950;143(4):329-36. [Medline].

  13. Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. Jan 21 2010;340:b5569. [Medline]. [Full Text].

  14. Ahmedin Jemal, DVM, PhD, Rebecca Siegel, MPH, Elizabeth Ward, et al. Cancer Statistics, 2008. CA Cancer J Clin. 2008;58:71-96. [Full Text].

  15. American Cancer Society. Cancer facts & figures 2008. Accessed December 21, 2010. Available at http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2008.

  16. Frank AL. Epidemiology of lung cancer. In: Roth JA, Ruckdeschel J, Weisenburger T, eds. Thoracic Oncology. Philadelphia, Pa: WB Saunders Co; 1989:6-15.

  17. Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. Oct 1 2006;24(28):4539-44. [Medline].

  18. zz.

  19. American Cancer Society. Cancer facts & figures 2009. Accessed December 21, 2010. Available at http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2009.

  20. American Cancer Society. Cancer facts & figures 2010. Accessed December 21, 2010. Available at http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-and-figures-2010.

  21. Arriagada R, Le Chevalier T, Pignon JP, Rivière A, Monnet I, Chomy P, et al. Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med. Dec 16 1993;329(25):1848-52. [Medline].

  22. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Small Cell Lung Cancer [serial online]. 2011;v.2. Available with free registration at www.nccn.org:Accessed May 21 2011. Available at http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf.

  23. [Guideline] Simon GR, Turrisi A. Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. Sep 2007;132(3 Suppl):324S-339S. [Medline]. [Full Text].

  24. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med. Jun 29 2011;[Medline].

  25. Zakowski MF. Pathology of small cell carcinoma of the lung. Semin Oncol. Feb 2003;30(1):3-8. [Medline].

  26. Hirsch FR, Matthews MJ, Aisner S, Campobasso O, Elema JD, Gazdar AF, et al. Histopathologic classification of small cell lung cancer. Changing concepts and terminology. Cancer. Sep 1 1988;62(5):973-7. [Medline].

  27. [Best Evidence] Amarasena IU, Walters JA, Wood-Baker R, Fong K. Platinum versus non-platinum chemotherapy regimens for small cell lung cancer. Cochrane Database Syst Rev. Oct 8 2008;CD006849. [Medline].

  28. Hanna NH, Einhorn LH. Small-cell lung cancer: state of the art. Clin Lung Cancer. Sep 2002;4(2):87-94. [Medline].

  29. Lally BE, Urbanic JJ, Blackstock AW, Miller AA, Perry MC. Small cell lung cancer: have we made any progress over the last 25 years?. Oncologist. Sep 2007;12(9):1096-104. [Medline].

  30. Schmittel A, Sebastian M, Fischer von Weikersthal L, et al. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. Aug 2011;22(8):1798-804. [Medline].

  31. Demetri G, Elias A, Gershenson D, Fossella F, Grecula J, Mittal B, et al. NCCN Small-Cell Lung Cancer Practice Guidelines. The National Comprehensive Cancer Network. Oncology (Williston Park). Nov 1996;10(11 Suppl):179-94. [Medline].

  32. Spigel DR, Townley PM, Waterhouse DM, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. Jun 1 2011;29(16):2215-22. [Medline].

  33. Klasa RJ, Murray N, Coldman AJ. Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung. J Clin Oncol. Mar 1991;9(3):499-508. [Medline].

  34. Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. Jul 15 2002;20(14):3054-60. [Medline].

  35. Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. Jan 28 1999;340(4):265-71. [Medline].

  36. [Best Evidence] Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. Aug 16 2007;357(7):664-72. [Medline].

  37. Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. Jan 10 2002;346(2):85-91. [Medline].

  38. Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. May 1 2006;24(13):2038-43. [Medline].

  39. Natale R, Lara P, Chansky K, et al. A randomized phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated extensive stage small cell lung cancer (E-SCLC). J Clin Oncol. 2008;26 (suppl):400s.

  40. Heigener D, Freitag L, Eschbach C et al. Topotecan/cisplatin (TP) compared to cisplatin/etoposide (PE) for patients with extensive disease-small cell lung cancer (ED-SCLC): final results of a randomised phase III trial. J Clin Oncol. 2008;26 (suppl):400s.

  41. Harris S, Chan MD, Lovato JF, Ellis TL, Tatter SB, Daniel Bourland J, et al. Gamma Knife Stereotactic radiosurgery as Salvage Therapy after Failure of Whole-Brain Radiotherapy in Patients with Small-Cell Lung Cancer. Int J Radiat Oncol Biol Phys. Feb 17 2012;[Medline].

  42. Jotte R, Conkling P, Reynolds C, Galsky MD, Klein L, Fitzgibbons JF, et al. Randomized phase II trial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy. J Clin Oncol. Jan 20 2011;29(3):287-93. [Medline].

  43. Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, et al. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. Oct 1994;12(10):2022-34. [Medline].

  44. Johnson BE, Bridges JD, Sobczeck M, Gray J, Linnoila RI, Gazdar AF, et al. Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide/cisplatin followed by cyclophosphamide, doxorubicin, and vincristine. J Clin Oncol. Mar 1996;14(3):806-13. [Medline].

  45. Johnson BE, Grayson J, Makuch RW, Linnoila RI, Anderson MJ, Cohen MH, et al. Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. J Clin Oncol. Mar 1990;8(3):396-401. [Medline].

  46. Lassen U, Osterlind K, Hansen M, Dombernowsky P, Bergman B, Hansen HH. Long-term survival in small-cell lung cancer: posttreatment characteristics in patients surviving 5 to 18+ years--an analysis of 1,714 consecutive patients. J Clin Oncol. May 1995;13(5):1215-20. [Medline].

 
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Table 1. 2008-2010 Estimates of New Cases of Lung Cancer and Estimates of Lung Cancer Deaths
Newly Diagnosed Cases of Diagnosed Lung Cancer Lung Cancer Deaths
2008 Estimates
Total (% of all cancers)215,020 (15%)161,840 (29%)
Men114, 69090,810
Women100,33071,030
2009 Estimates
Total (% of all cancers)219,440 (15%)159,390 (28%)
Men116,09088,900
Women103,35070,490
2010 Estimates
Total (% of all cancers)222,520 (15%)157,300 (28%)
Men116,75086,220
Women105,77071,080
Sources: American Cancer Society. Cancer facts & figures 2008,[15] 2009,[19] 2010.[20]
Table 2. Paraneoplastic Syndromes
Organ System Syndrome Mechanism Frequency
EndocrineSIADHAntidiuretic hormone5-10%
Ectopic secretion of ACTHAdrenocorticotropic hormone5%
Atrial natriuretic factor
NeurologicEaton-Lambert reverse myasthenic syndrome5-6%
Subacute cerebellar degeneration
Subacute sensory neuropathy
Limbic encephalopathyAnti-Hu, Anti-Yo antibodies
ACTH = adrenocorticotropic hormone; SIADH = syndrome of inappropriate antidiuretic hormone.
Table 3. Commonly Used Chemotherapy Regimens in Small Cell Lung Cancer
Regimen Dose
“CAV” Regimen
Cyclophosphamide1000 mg/m2 IV day 1
Doxorubicin (Adriamycin)50 mg/m2 IV day 1
Vincristine2 mg IV
“PE” Regimen
Cisplatin25 mg/m2 IV days 1-3
Etoposide100 mg/m2 IV days 1-3
“CAVE” Regimen
Cyclophosphamide1000 mg/m2 IV day 1
Doxorubicin (Adriamycin)50 mg/m2 IV day 1
Vincristine1.4 mg/m2 IV day 1 (maximum 2 mg)
Etoposide100 mg/m2 IV day 1
“PEC” Regimen
Paclitaxel200 mg/m2 IV day 1
Etoposide50 mg/d PO alternating with



100 mg/d PO from days 1-10



CarboplatinAUC 6 IV day 1
Single-Agent Regimens
Topotecan1.5 mg/m2 IV day 1-5
Etoposide50 mg PO bid days 1-14
AUC = area under the concentration curve; bid = twice daily; IV = administered intravenously; PO = administered orally.
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