Chemotherapy etoposide

JP is receiving a highly myelosuppressive chemotherapy regimen for the next 3 days for his lymphoma. The chemotherapy orders specify ifosfamide, carboplatin, and etoposide. The goal of this cycle of chemotherapy is to put the cancer into remission so that his lymphoma can be cured with a bone marrow transplant. 

The rapidly proliferating cells of the GI tract make them susceptible to the effects of chemotherapy. Mucositis is the inflamed, ulcerated mucosa of the mouth, esophagus, and lower GI tract that may result in infection and pain with subsequent decreased fluid and nutritional intake. Methotrexate, 5-FU, etoposide, and doxorubicin are the chemotherapy agents most commonly associated with mucositis. Patients should be instructed on good oral mouth care and use saline rinses several... 

Risk factors for the development of AML include exposure to environmental toxins, Hispanic ethnicity, and genetics.6 Of greater concern is the increased prevalence of AML as a secondary malignancy, resulting from chemotherapy and radiation treatment for other cancers. Alkylating agents, such as ifosfamide and cyclophosphamide, and topoisomerase inhibitors, such as etoposide, are linked to an increased risk of myelodysplastic syndrome (MDS) and AML.8... 

Dexa-BEAM dexamethasone/ carmustine (BCNU)/ etoposide (VP-16)/ cytarabine (Ara-C)/ melphalan Dexamethasone 8 mg PO Q8H days 1 -10 BCNU 60 mg/M2 IV day 2 VP-16 75 mg/M2 IV days 4-7 Ara-C 100 mg/M2 IVQ12H days 4-7 Melphalan 20 mg/M2 IV day 3 REF Pfreundschuh etal. J Clin Oncol 1994 12 580-586 PREMEDICATIONS 1. Kytril 1 mg PO/IV 30 minutes before and 12 hours after chemotherapy on days 2 and 3 2. Compazine 10 mg PO/IV 30 minutes before chemotherapy on days 4-7 OTHER MEDICATIONS 1. Give non-cisplatin delayed emesis prophylaxis Repeat every 28 days Carmustine—maximum total dose is 1440 mg/M2 causes delayed myelosuppression... 

Standard combination regimens (e.g., CHOP) yield disappointing results. Newer approaches including dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), and rituximab-containing combination chemotherapy are promising. 

Aprepitant is a substrate, a moderate inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9. Use aprepitant with caution in patients receiving concomitant medicinal products, including chemotherapy agents that are primarily metabolized through CYP3A4 (docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine). 

The earliest combination chemotherapy and radiation trials in nonsmall-cell lung cancer included cisplatin and 5-fluorouracil and concurrent radiation therapy and found survival results comparable to those for sequential chemotherapy and radiation or to daily cisplatin and radiation therapy without surgery (119,121). Phase II studies of stage Ilia and Illb nonsmall-cell lung cancer patients treated with the combination of cisplatin with etoposide and 5 -fluorouracil and either single daily radiation fractionation or twice daily radiation fractionation prior to surgery produced similar clinical results (119,121). Complete surgical resection was accomplished in 70% of the patients, the median survival was 22 mo and the 2-yr survival rate was 45%. 

CyEP, cyclophosphamide/etoposide/cisplatin EP, etoposide/cisplatin NCI, National Cancer Institute PIM, cisplatin/ifosfarnide/mitomycin VdP, vindesine/ cisplatin preop., preoperatively postop., postoperatively ChT, chemotherapy NS, not significant. 

Keller S, Adak S, Fossella F, et al. Randomized prospective comparison of adjuvant mediastinal radiation with or without concurrent chemotherapy with cisplatin and etoposide for patients with completely resected T1-3N1-2M0NSCLC US intergroup lung trial 0115. Proc Am Soc Thera Rad Oncol (ASTRO). IJROBP 45, 1999 (abstr). 

A Japanese trial compared sequential delivery of chemotherapy and radiation therapy to concurrent delivery of chemotherapy and radiation (47). Patients were randomized to receive concurrent hyperfractionated radiation therapy (d 2 of cycle 1 of chemotherapy) or to sequential chemotherapy followed after the fourth cycle by hyperfractionated radiation therapy. The radiation dose was45 Gygivenin 1.5 Gy fractions twice daily for a total of 30 fractions in 3 wk. The chemotherapy given was cisplatin and etoposide. The median survival for the concurrent schedule was 29 mo and for the sequential schedule was 19 mo. The 2-yr survival was 50% for the concurrent therapy and 40% for the sequential therapy (47). These results favored concurrent therapy and are the best results to date for patients with LD-SCLC. 

Other studies evaluated the question of whether early delivery of radiation concurrently with chemotherapy was better than late delivery. A study performed by the C ALGB randomized patients to early (d 1, cycle 1), late (d 64, cycle 4), or no radiation therapy. The radiation therapy dose was 50 Gy over 6 wk. Chemotherapy used in this trial was cyclophosphamide, etoposide, and vincristine. The local recurrence rate for the early, late, and no radiation therapy arms was 49%, 68%, and 82%, respectively. The 2-yr progression-free survival rate was 15% for the early schedule arm vs 25% for the late schedule (p = 0.078). The 5-yr survival rate for the early, late, and no radiation therapy arms was 6.6%, 12%, and 3%, respectively (p = 0.007). The poor 5-yr survival rate for the early schedule was felt to be due to the significant decrease in chemotherapy dose needed for the early schedule group (4,49). 

The NCIC randomized patients to radiation therapy started either early or late with concurrent chemotherapy (cyclophosphamide, doxorubicin, and vincristine alternating with cisplatin and etoposide) (6). The radiation therapy dose was 40 Gy given in 15 fractions over three weeks with the cisplatin and etoposide portion of the chemotherapy. In the early arm the radiation was started on d 21 of cycle 2 (after the first cycle... 

Gy in eleven fractions followed by a cycle of cisplatin and etoposide followed by the same schedule of radiation and followed again by chemotherapy. The delayed radiation arm gave the chemotherapy first then started the radiation therapy in wk 18 and again in wk 23. The same chemotherapy and radiation doses were given. The 5-yr survival and local recurrence rate were not statistically different. The 5-yr survival for the early arm was 10.8% vs 12% for the delayed radiation therapy arm. The local recurrence rate for the early radiation arm was 76.6% vs 72.8% for the delayed arm (50). 

The EORTC randomized patients to either start radiation therapy during wk 6 (early) or after the chemotherapy during wk 14 (late). The chemotherapy regimen used was cyclophosphamide, doxorubicin, and etoposide. The dose of radiation given in the early arm was 50 Gy in 20 fractions in 89 d. The dose of radiation given in the late arm was 50 Gy in 20 fractions in 26 d. No significant differences were noted for local recurrence (50.5% early radiation vs 45.5% late radiation) or 3-yr survival (14% for both early and late radiation therapy) (51). 

Johnson BE, Salem C, Nesbit J, et al. Limited stage small-cell lung cancer (SCLC) treated with concurrent BID chest radiotherapy (RT) and etoposide, cisplatin (VP/PT) followed by chemotherapy (CT) selected by in vitro drug sensitivity testing (abstract 818). ProcAm Soc Clin Oncol 1991 10 240. 

Metastatic osteosarcoma has a poor prognosis unless the disease is confined to the lungs and is resectable. Palliative chemotherapy can be employed with a number of drugs including doxorubicin, cisplatin, carboplatin, methotrexate, ifosfamide and etoposide. 

Three classes of plant-derived drugs, the vinca alkaloids (vincristine, vinblastine, and vinorelbine), the epipodo-phyllotoxins (etoposide and teniposide and the tax-anes (paclitaxel and taxotere), are used in cancer chemotherapy. These classes differ in their structures and mechanisms of action but share the multidrug resistance mechanism, since they are all substrates for the multidrug transporter P-glycoprotein. 

Another area in which natural products have had a major impact on longevity and quality of life is in the chemotherapy of cancer. In fact, most major anticancer drugs are derived from plants or microorganisms (see Chapter 62). Examples include bleomycin, doxorubicin, daunorubicin, vincristine, vinblastine, mitomycin, streptozocin, and most recently, additions of paclitaxel (Taxol ), ironotecan (a camptothecin derivative), and etoposide and tenoposide (podophyllo-toxin derivatives). 

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