Etoposide small-cell lung carcinoma

Levitan N, Dowlati A, Shina D, et al. Multi-institutional phase ITU trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung carcinoma. J Clin Oncol 2000 18(5) 1102-1109. 

Small cell lung carcinoma Multiple combinations that include cyclophosphamide, cisplatin, doxorubicin, etoposide, and vincristine... 

In 8 patients with extensive small cell lung carcinoma the pharmacokinetics of a 100-mg oral dose of etoposide were unaffected when it was taken with a full breakfast, when compared with the fasting state. However, the manufacturer recommends that etoposide should be taken on an empty stomach. ... 

Short term treatment with TPA sensitized human 2008 ovarian carcinoma cells to cis-platin. This sensitization disappeared completely by seven hours after treatment, indicating that not inhibition, but activation of PKC sensitizes 2008 cells to the antiproliferative activity of cis-platin (Isonishi et al., 1990). Pretreatment of HeLa cells with TPA or PdBu caused a 9-fold increase in cellular sensitivity to cis-platin and 2.5-fold to melphalan, but had now effect on the antiproliferative activity of bleomycin, adriamycin, vincristine, or mitomycin C. The sensitization of HeLa cells by TPA was associated with a 6-fold stimulation of PKC activation and a concentration- and time-dependent increase in cellular platinum content. (Basu et al. 1990). PKC activity was found to be decreased significantly in cis-platin-resistant human small cell lung H69/CP cancer cells compared to the drug-sensitive variant. A similar reduction in PKC activity was noted in ovarian carcinoma 2008 cells that were resistant to cis-platin. A modest decrease in PKC activity was also observed in etoposide-resistant H69 cells but not in taxol-resistant H69 cells or bleomycin-resistant human head and neck carcinoma A-253 cells (Basu et al., 1996), indicating that reduced PKC activity leads to decreased sensitivity in this system. 

A semisynthetic podophyllotoxin derivative, VP 16213 (etoposide), has been approved in the United States as a chemotherapeutic agent (often in combination regimes with cisplatin, bleomycin, and others) for the treatment of refractory testicular tumors and for the treatment of small cell lung cancer. VM26 (teniposide) is being investigated for the treatment of acute lymphoblastic leukemia, various lymphomas, and other carcinomas. Semisynthetic derivatives are being used in Europe for the treatment of psoriasis and rheumatoid arthritis. 

Ratain MJ, Kaminer LS, Bitran JD, Larson RA, Le Beau MM, Skosey C, Purl S, Hoffman PC, Wade J, Vardiman JW, et al. Acute nonlymphocytic leukemia following etoposide and cisplatin combination chemotherapy for advanced non-small-cell carcinoma of the lung. Blood 1987 70(5) 1412-17. 

The intravenous dose (Vepesid, Toposar, Etopophos) for testicular cancer in combination therapy is 50 to 100 mg/m for 5 days, or 100 mg/m on alternate days for three doses. For small-cell carcinoma of the lung, the dose in combination therapy is 50 to 120 mo/m per day intravenously for 3 days, or 50 mg per day orally for 21 days. Cycles of therapy usually are repeated every 3 to 4 weeks. When given intravenously, the drag should be administered slowly during a 30- to 60-minute infusion to avoid hypotension and bronchospasm, which likely result from the additives used to dissolve etoposide, a relatively insoluble compound. 

Etoposide is used primarily in treatment of testicular tumors in combination with bleomycin and cispiatin, and in combination with cispiatin and ifosfamide for small-cell carcinoma of the lung. It also is active against non-Hodgkin s lymphomas, acute nonlymphocytic leukemia, and Kaposi s sarcoma associated with AIDS. Etoposide has a favorable toxicity profile for dose escalation in that its primary acute toxicity is myelosuppression. In combination with ifosfamide and carboplatin, it is frequently used for high-dose chemotherapy in total doses of 1500 to 2000 mg/m. ... 

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