equired for the generation of the biologically active species and while metabolism is extensive, it is also quite variable among patients.
In a study at Indiana University, 50 fully eva luable patients with germ cell testicular cancer were treated with IFEX in combination with cisplatin and either vinblastine or etoposide after failing (47 of 50 patients) at least two prior chemotherapy regimens consisting of cisplatin/vinblastine/bleomycin, (PVB), cisplatin/vinblastine/actinomycin D/bleomycin/cyclophosphamide, (VAB6), or the combination of cisplatin and etoposide. Patients were selected for remaining cisplatin sensitivity because they had previously responded to a cisplatin containing regimen and had not progressed while on the cisplatin containing regimen or within 3 weeks of stopping it. Patients served as their own control based on the premise that long term complete responses could not be achieved by retreatment with a regimen to which they had previously responded and subsequently relapsed.
Ten of 50 fully eva luable patients were still alive 2 to 5 years after treatment. Four of the 10 long term survivors were rendered free of cancer by surgical resection after treatment with the ifosfamide regimen; median survival for the entire group of 50 fully eva luable patients was 53 weeks.
INDICATIONS AND USAGE
IFEX, used in combination with certain other approved antineoplastic agents, is indicated for third line chemotherapy of germ cell testicular cancer. It should ordinarily be used in combination with a prophylactic agent for hemorrhagic cystitis, such as mesna.
CONTRAINDICATIONS
Continued use of IFEX is contraindicated in patients with severely depressed bone marrow function (see WARNINGS and PRECAUTIONS sections). IFEX is also contraindicated in patients who have demonstrated a previous hypersensitivity to it.
WARNINGS
Urinary System
Urotoxic side effects, especially hemorrhagic cystitis, have been frequently assciated with the use of IFEX.
It is recommended that a urinalysis should be obtained prior to each dose of IFEX. If microscopic hematuria (greater than 10 RBCs per high power field), is present, then subsequent administration should be withheld until complete resolution.
Further administration of IFEX should be given with vigorous oral or parenteral hydration.
Hematopoietic System
When IFEX is given in combination with other chemotherapeutic agents, severe myelosuppression is frequently observed. Close hematologic monitoring is recommended. White blood cell (WBC) count, platelet count and hemoglobin should be obtained prior to each administration and at appropriate intervals. Unless clinically essential, IFEX should not be given to patients with a WBC count below 2000/µL and/or a platelet count below 50,000/µL.
Central Nervous System
Neurologic manifestations consisting of somnolence, confusion, hallucinations and in some instances, coma, have been reported following IFEX therapy. The occurrence of these symptoms requires discontinuing IFEX therapy. The symptoms have usually been reversible and supportive therapy should be maintained until their complete resolution.
Pregnancy
Animal studies indicate that the drug is capable of causing gene mutations and chromosomal damage in vivo. Embryotoxic and teratogenic effects have been observed in mice, rats and rabbits at doses 0.05 to 0.075 times the human dose. Ifosfamide can cause fetal damage when administered to a pregnant woman. I |
