Ethyol

In Patients with Ovarian Cancer

ETHYOL® (amifostine) pretreatment selectively protects against renal toxicity in patients with ovarian cancer

The risk of nephrotoxicity remains high9

  • Nephrotoxicity, specifically acute kidney injury (AKI), affects approximately 30% of patients receiving cisplatin therapy, even after a single dose9,10
    • AKI is an independent risk for mortality and can potentially increase the risk of death up to 15-fold10
  • Renal toxicity remains a serious problem despite aggressive regimens of intravenous hydration11

  • Less than 2% of patients pretreated with ETHYOL experienced dose-limiting toxicities—defined as serum creatinine levels ≥1.5 mg/dL or CRCL ≤65 mL/min—as compared to 12.5% of patients receiving cisplatin and cyclophosphamide alone (P=0.001)11
  • Consistent with the cumulative nature of cisplatin-induced nephrotoxicity, the differences become more pronounced in the latter cycles of chemotherapy11
    • Only 10% of patients pretreated with ETHYOL required a treatment delay or discontinuation by cycle 6 vs 36% of patients receiving CP alone (P=0.003)
    • By the last cycle, just 13% of patients pretreated with ETHYOL experienced ≥40% reduction from baseline creatinine clearance vs 30% of patients receiving CP alone (P=0.001)

ETHYOL has no detectable effect on the efficacy of CP chemotherapy11

  • Median survival time of patients in both treatment arms was 31 months11
  • The most common side effects reported by patients receiving ETHYOL were nausea and/or vomiting, and hypotension characterized by a transient decrease in blood pressure11
  • Flushing, sneezing not associated with other signs of allergic reaction, dizziness, sleepiness, hiccups, and chills were also more commonly seen in patients receiving ETHYOL—but these effects did not interfere with therapy11
Kemp study design: In this controlled, multicenter study, 242 female patients with stage III or IV epithelial ovarian cancer were randomized to receive either cisplatin and cyclophosphamide with ETHYOL (n=122) or cisplatin and cyclophosphamide alone (n=120). The primary end point was the protective effects of ETHYOL against hematologic toxicity. Nephrotoxicity was evaluated by the need to delay or discontinue the dose of cisplatin. Median follow-up time was more than 41 months.11

References:
1. ETHYOL [prescribing information]. Nashville, TN; Cumberland Pharmaceuticals Inc.; May 2017. 8. Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 Clinical Practice Guideline Update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27(1):127-145. 9. Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 2008;73(9):994-1007. 10. Ozkok A, Edelstein CL. Pathophysiology of cisplatin-induced acute kidney injury. Biomed Res Int. 2014: 967826. 11. Kemp G, Rose P, Lurain J, et al. Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol. 1996;14(7):2101-2112.

Indication: ETHYOL (amifostine) is indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer.

ETHYOL is indicated to reduce the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands.

IMPORTANT DOSAGE AND ADMINISTRATION INSTRUCTIONS
Patients should be adequately hydrated prior to ETHYOL infusion. Blood pressure should be monitored prior to, during and immediately after infusion. Antiemetic medication should be administered prior to and in conjunction with ETHYOL.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS

ETHYOL is contraindicated in patients with known hypersensitivity to aminothiol compounds.

WARNINGS AND PRECAUTIONS
ETHYOL should not be administered in patients receiving chemotherapy for other malignancies in which chemotherapy can produce a significant survival benefit or cure. ETHYOL should not be administered in patients receiving definitive radiotherapy, since there are at present insufficient data to exclude a tumor-protective effect in this setting.

Patients who are hypotensive or in a state of dehydration should not receive ETHYOL. Patients should have antihypertensive therapy interrupted 24 hours preceding administration of ETHYOL. Patients should not receive ETHYOL where therapy cannot be stopped for 24 hours preceding treatment.

The fluid balance of the patient should be carefully monitored when ETHYOL is administered with highly emetogenic chemotherapy.

Fatal and serious cutaneous reactions such as Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, toxicoderma, exfoliative dermatitis and drug reaction with biopsy-confirmed eosinophilia and systemic symptoms (DRESS) have been reported with ETHYOL treatment. These reactions is higher in patients receiving ETHYOL as a radioprotectant. Serious cutaneous reactions may develop weeks after initiation of ETHYOL administration. Discontinue Ethyol for cutaneous reactions or mucosal lesions appearing outside the injection site or radiation port and for erythematous, edematous or bullous lesions on the palms or soles. Monitor patients carefully prior to, during and after ETHYOL administration. In case of severe acute allergic reactions ETHYOL should be immediately and permanently discontinued. Epinephrine and other appropriate measures should be available for treatment of serious allergic events such as anaphylaxis.

ADVERSE REACTIONS
In a randomized study of patients with ovarian cancer given ETHYOL, the most common adverse events included transient hypotension, nausea, vomiting, and a decrease in serum calcium concentrations. Other adverse events reported in clinical studies involving patients with ovarian or head and neck cancers include hypersensitivity and anaphylactic reactions, flushing, chills, malaise, pyrexia, diplopia, blurred vision, rash, dizziness, somnolence, hiccups, diarrhea, and sneezing. Injection site reactions including pruritus and urticaria were also observed.

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