Abstract
From January 1983 through August 1988, 318 consecutive patients with refractory germ cell neoplasms were treated with ifosfamide-containing combination chemotherapy. The patients received ifosfamide at 1.2 gm/m2 day with cis-platin 20 mg/m2 day for 5 days and etoposide 75 mg/m2 day for 5 days or vinblastine 0.11 mg/kg on days 1 and 2 for each cycle. Of 277 evaluable patients, NAC was used as an uroprotector in the initial 86 patients while the latter 191 consecutive patients received mesna to reduce urothelial toxicity. Dosages of NAC was 2.0 gm po q 6 hr and for mesna 120 mg/m2 IV push prior to ifosfamide and then 1200 mg/m2/day as continuous infusion of 5 consecutive days. All patients received 3.0 liters of normal saline per day. The number of courses of chemotherapy given in the two groups were similar. Twenty-four of the 86 patients (27.9%) receiving NAC developed hematuria (13 patients — grade 1, 4 patients — grade 2, and 7 patients — grade 3 toxicity). While 8 out of 191 (4.2%) mesna patients developed hematuria (6 — grade 1 and 2 — grade 3) (p<0.0001). The incidence of severity of renal toxicity was similar in the two groups. Ifosfamide dosage was reduced solely for urothelial toxicity in 11 patients receiving NAC compared with none of the patients receiving mesna (p<0.0001). Chemotherapy response was similar in the two groups. In conclusion, mesna provides better urothelial protection from ifosfamide-induced toxicity than NAC and allows better maintenance of the drug dosage.
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References
Brock N: The oxazaphosphorines. Cancer Treat Rev 10 (Suppl A:3–1), 1989
Brade WP, Merdrich K, Varini M: Ifosamide-pharmacology, safety and therapeutic potential. Cancer Treat Rev 12:1–47, 1985
Brock N: Oxazaphosphorine cytostatics: past-present-future. Seventh Cain Memorial Award lecture (Review), Cancer Res 49(1):1–7, 1989
Marti C, Steiner R, Viollier AF: Systemic application of uromitexan to reduce urotoxicity. Contrib Oncol 5:57–59, 1981
Morgan LR, Posey LE, Rainey J, Bickers J, Ryan D, Vial R, Hull EW: Ifosfamide: A weekly dose fractionated schedule in bronchogenic carcinoma. Cancer Treat Rep 65:693–695, 1981
Gad-El-Mawla N, Ziegler JL: Ifosfamide treatment of pancreatic cancer. Cancer Treat Rep 65(3–4):357–358, 1981
Kovach JSet al.: A phase 2 study of intermittent high dose isophosphamide therapy of advanced colorectal cancer. Oncology 29:34–39, 1974
Ahmann DL, Hahn RG, Bisel HF: A phase II evaluation of ifosfamide (NSC 109 724) treatment of disseminated breast cancer. Proc Am Assoc Cancer Res 15:1982, Abstr 794,1974
Brock N, Pohl J, Stekar J: Studies on the urotoxicity of oxazaphosphorine cytostatics and its prevention. 2. Comparative study on the uroprotective efficacy of thiols and other sulfur compounds. Eur J Cancer Clin Oncol 17(11):1155–1163, 1981
Morgan LR, Donley PJ, Harrison EFet al.: Protective effect of N-acetylcysteine on urotoxicity produced by oxazaphosphorine without interference with anti-cancer activity. Eur J Cancer Clin Oncol (Letter) 18:113–114, 1982
Scheef W, Klein HO, Burkert H, Gunther U, Hoefer-Janker H, Mitrenga D, Schnitker J, Voigtmann R: Controlled clinical studies with an antidote against the urotoxicity of oxazaphosphorines: preliminary results. Cancer Treat Rep 63:501–505, 1979
Bryant BM, Jarman M, Ford HT, Smith IE: Prevention of isophosphamide-induced urothelial toxicity with 2-mercaptoeterane supleonate sodium (mesnum) in patients with advanced carcinoma. Lancet 2:657–659, 1980
Varini M, Ficarra G, Monfardini S: Ifosfamide treatment with and without the uroprotective agent mesna. 12th International Congress of Chemotherapy, Florence, Abstr 176, 1981
Loehrer PJ, Williams SD, Einhorn LH: VP-16 plus ifosfamide plus cisplatin as salvage therapy in refractory germ cell cancer. J Clin Oncol 4:528–536, 1986
Slavik M, Saiers J: Phase II clinical study of acetylcysteines preventing ifosfamide induced hematuria. Semin Oncol (Suppl) 10:62–65, 1983
Shaw IC, Graham MI: Mesna — a short review. Cancer Treat Rev 14:67–86, 1987
Wheeler BM, Loehrer PJ, Williams SD, Einhorn LH: Ifosfamide in refractory male germ cell tumors. J Clin Oncol 4:28–34, 1986
Loehrer PJ, Williams SD, Einhorn LH, Ansari R: Ifosfamide: An active drug in the treatment of adenocarcinoma of the pancreas. J Clin Oncol 3:367–372, 1985
Loehrer PJ, Williams SD, Nichols CR: Ifosfamide plus 5-Fluorouracil for the treatment of adenocarcinoma of the pancreas. Cancer Treat Rep 71:1115–1116, 1987
Nichols CR, Loehrer PJ, Greist A, Kubilis PS, Hoffman R: Salvage chemotherapy for lymphoma with VP-16, ifosfamide and cisplatin. Med Ped Oncol 16:12–16, 1988
Loehrer PJ, Birch R, Kramer B, Greco FA, Einhorn LH: Ifosfamide plus N-acetylcysteine in the treatment of small cell and non-small cell carcinoma of the lung: A Southeastern Cancer Study Group trial. Cancer Treat Rep 70: 919–920, 1986
Scheulen ME, Bremer K, Niederle N, Kriswchke W, Higi M, Seeber S, Schmidt CG: Ifosfamide and etoposide in refractory testicular tumors. In: UICC Conference on Clinical Oncology, p 129, Abstr 15-0373, 1981
Legha S, Papadopoulos N, Plager C: A comparative evaluation of the uroprotective effect of mercaptoethane sulfonate and N-acetylcysteine in sarcoma patients treated with ifosfamide. Proc Am Soc Clin Oncol 9:311 (Abstr), 1990
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Munshi, N.C., Loehrer, P.J., Williams, S.D. et al. Comparison of N-acetylcysteine and mesna as uroprotectors with ifosfamide combination chemotherapy in refractory germ cell tumors. Invest New Drugs 10, 159–163 (1992). https://doi.org/10.1007/BF00877240
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DOI: https://doi.org/10.1007/BF00877240