Ifex/Mesnex Kit

Generic Name: Ifosfamide
Class: Antineoplastic Agents
VA Class: AN100
CAS Number: 3778-73-2

• 
  

  Administer only under supervision of qualified clinicians experienced in the use of cancer chemotherapeutic agents.^a

  
  


• 
  

  Hemorrhagic cystitis may occur and may require discontinuance of therapy (See Bladder Toxicity under Cautions).^a

  
  


• 
  

  Severe neurotoxicity (e.g., confusion, coma) may occur and may require discontinuance of therapy (See Nervous System Effects under Cautions).^a

  
  


• 
  

  Severe myelosuppression reported (See Hematologic Effects under Cautions).^a

  
  

Introduction

Antineoplastic agent; alkylating agent structurally related to cyclophosphamide.^{1 2 3 96 103 111 112}

Uses for Ifex/Mesnex Kit

Testicular Cancer

Component of various chemotherapeutic regimens as third-line therapy for recurrent or refractory germ cell testicular cancer¹ (designated an orphan drug by FDA for this use).⁵

Soft Tissue Sarcomas

Component of various chemotherapeutic regimens in conjunction with surgery and/or radiation therapy in the treatment of various soft tissue sarcomas†^{2 3 9 33 34 35 36 37 38 39 40 41 42 43 44 45 46 111} (designated an orphan drug by FDA for this use).⁵

Osteosarcoma

Used alone or in conjunction with other drugs (e.g., etoposide)^{9 35 36 37 40 41 42} for treatment of localized, metastatic, and recurrent osteosarcoma†^{9 37 40 41} (designated an orphan drug by FDA for this use).⁵

Bladder Cancer

Used alone^{9 143} or in combination with other antineoplastic agents^{144 145 146 147} for treatment of advanced or metastatic bladder cancer†.¹⁴³

Small Cell Lung Cancer

Treatment of small cell lung cancer† as part of a combination regimen.^{2 3 8 9 10 11 12 13 54 132}

Cervical Cancer

Component of various combination regimens (e.g., cisplatin and ifosfamide with or without bleomycin) for the treatment of metastatic or recurrent cervical cancer†.^{3 9 20 21 22 23 25 152 153 154 155 156 157 158}

Ovarian Cancer

Used alone or in conjunction with other antineoplastic agents for second-line (salvage) therapy in patients with advanced or recurrent ovarian carcinoma†.^{9 26 28 29 135}

Non-Hodgkin's Lymphoma

Treatment of advanced small noncleaved cell lymphoma (Burkitt’s and non-Burkitt’s) in children^{9 119} as part of a combination regimen.^c

Ifex/Mesnex Kit Dosage and Administration

General

• 
  

  Consult specialized references for procedures for proper handling and disposal of antineoplastics.¹

  
  


• 
  

  Adequately hydrate patient prior to and during ifosfamide therapy (e.g., 2 L of oral or IV fluid daily) to minimize urotoxicity.^{1 2 58 59 141}

  
  


• 
  

  Concomitant therapy with a uroprotective agent (e.g., mesna) recommended during ifosfamide therapy to decrease the incidence of bladder toxicity.^{1 2 58 59 95 141 160} (See Bladder Toxicity under Cautions.)

  
  

Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by slow IV infusion.¹

Handle cautiously (e.g., use protective gloves);¹ avoid exposure during handling and preparation of IV solution.¹ If skin or mucosal contact occurs, immediately wash skin with soap and water and flush mucosa with water.¹

IV Administration

Reconstitution

Reconstitute vial containing 1 or 3 g of ifosfamide powder with 20 or 60 mL, respectively, of sterile or bacteriostatic water for injection, to provide a solution containing 50 mg/mL.^a

Shake well to ensure complete dissolution.^a May be infused directly or further diluted prior to IV infusion.^a

Dilution

May be diluted with 5% dextrose injection, 0.9% sodium chloride injection, lactated Ringer’s injection, or sterile water for injection to a concentration of 0.6–20 mg/mL.^a

Rate of Administration

Administer as a slow IV infusion over a period of ≥30 minutes.^a

Dosage

Consult published protocols for the dosage of ifosfamide and other chemotherapeutic agents and the method and sequence of administration.^b

Adults

Testicular Cancer

IV

1.2 g/m² daily for 5 consecutive days.^a Repeat course of therapy every 3 weeks (or following recovery of patient’s hematologic functions to within acceptable limits), usually for a total of 4 courses.^a

Cautions for Ifex/Mesnex Kit

Contraindications

• 
  

  Severe bone marrow depression.¹

  
  


• 
  

  Known hypersensitivity to ifosfamide or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Bladder Toxicity

Hemorrhagic cystitis, hematuria, dysuria, and urinary frequency reported frequently.^a Hemorrhagic cystitis can be severe and may be fatal.⁹⁵

Attributed to chemical irritation by metabolites (e.g., acrolein) that accumulate in concentrated urine.^{1 2 3 38 59 111}

Reduce bladder toxicity with conventional uroprophylaxis (e.g., high fluid intake, frequent urination) and use of fractionated ifosfamide dosage schedule, and concurrent administration of mesna.^{1 2 3 59 110}

Examine urine prior to administration of each ifosfamide dose for presence of erythrocytes, which may precede hemorrhagic cystitis.^{a 95}

If microscopic hematuria is present (>10 erythrocytes per high power field [HPF]), discontinue ifosfamide until complete resolution;^a use vigorous oral or parenteral hydration as well as mesna for subsequent courses of ifosfamide.^{1 141}

Discontinue ifosfamide or reduce dosage in patients who develop hematuria (>50 erythrocytes/HPF) while receiving usual dosages of ifosfamide in conjunction with mesna.⁹⁵

Hematologic Effects

Dose-dependent myelosuppression, principally leukopenia and, to a lesser extent, thrombocytopenia, occurs commonly.^{1 2 3 58 59}

Carefully monitor hematologic status during therapy; evaluate leukocyte and platelet counts and hemoglobin concentrations prior to and at appropriate intervals during therapy.^{1 2 3 58 59} Do not administer ifosfamide if leukocyte count <2000/mm³ and/or platelet count <50,000/mm³.¹ In general, withhold subsequent courses until leukocyte count >4000/mm³ and platelet count >100,000/mm³.¹

Use with caution in patients with compromised bone marrow reserve (i.e., leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents).¹

Nervous System Effects

Risk of neurotoxicity, characterized by somnolence, confusion, encephalopathy, coma, confusion, mutism, auditory and/or visual hallucinations, and stupor.^{1 2 3 36 58 59 82 84 86 87 126 128}

If one or more signs of serious neurotoxicity (i.e., somnolence, confusion, hallucinations, and/or coma) occur during therapy, discontinue therapy and institute appropriate supportive therapy.^{1 82 142} Effects generally are reversible and resolve within 2–4 days.^{1 2 3 36 58 59 80 82 83 84 85 128}

Fetal/Neonatal Morbidity and Mortality

Can cause fetal harm; teratogenicity and embryotoxicity demonstrated in animals.^a

If used during pregnancy or patient becomes pregnant, apprise of potential fetal hazard.¹

Major Toxicities

Renal Effects

Potentially serious nephrotoxicity (e.g., acute or chronic renal failure, Fanconi’s syndrome, renal tubular acidosis, nephrogenic diabetes insipidus); may be evidenced by aminoaciduria, glycosuria, proteinuria, cells or casts in the urine, increase in S_cr or BUN, or decreased Cl_cr.^{1 3 19 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 96 124}

Nephrotoxicity may develop during therapy or following discontinuance of the drug and can be reversible.^{62 64 67 68 69 70 72 74 76 77 122}

Increased risk of nephrotoxicity associated with previous or concurrent cisplatin therapy and in patients with preexisting renal impairment, infiltrating renal tumor, or prior nephrectomy.^{3 19 59 62 64 67 68 73 74 76 110 124 125}

Electrolyte Disturbances

Potentially fatal electrolyte abnormalities and/or acidosis reported.⁶⁵ Closely monitor serum and urine chemistries (i.e, phosphorus, potassium, alkaline phosphatase) and other appropriate laboratory studies.^{1 62 65 68 77 141} If electrolyte abnormalities develop, institute appropriate therapy to correct any imbalance(s).^{1 62 65 68 77}

General Precautions

Wound Healing

May interfere with normal wound healing.^a

Specific Populations

Pregnancy

Category D.^a (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established.¹

Has been used in children 15 days to 17 years of age for the treatment of certain malignancies (e.g., Ewing’s sarcoma, rhabdomyosarcoma, Wilms’ tumor); adverse effects reported in these children appear to be similar to those reported in adults.^{34 61 62 75 121 122 133}

Children ≤5 years of age may be more susceptible to ifosfamide-induced renal toxicity than older children or adults.^{3 62 64}

Geriatric Use

Select dosage based on the clinical, renal, and hematologic response and tolerance of the patient; consider age-related decrease in hepatic, renal and/or hematopoietic function.¹

Renal Impairment

Use with caution.^a Possible increased risk of nephrotoxicity^{3 19 59 62 64 67 68 73 74 76 110 124 125} and neurotoxicity.^{1 2 3 36 58 59 82 86} (See Nervous System Effects under Cautions.)

Common Adverse Effects

Alopecia,^{1 59} nausea/vomiting,^{1 2 3 36} hematuria, CNS toxicity, infection, renal impairment.^{1 a}

Interactions for Ifex/Mesnex Kit

Converted to active metabolites by mixed-function oxidases (cytochrome P-450 system).^{2 3 103 111}

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (increased or decreased metabolism of ifosfamide); may result in increased or decreased conversion to active metabolites.^{2 79 96 141}

Specific Drugs

Drug	Interaction	Comments
Cisplatin	Increased risk of nephrotoxicity 3 19 59 62 64 67 68 73 74 76 110 124 125	Associated with previous or concurrent cisplatin therapy3 19 59 62 64 67 68 73 74 76 110 124 125
Mesna	Interacts chemically with urotoxic ifosfamide metabolites and precursors to prevent or decrease incidence and severity of bladder toxicity (e.g., hemorrhagic cystitis)2 3 62 63 71 95 108 141	Used for uroprotection2 3 62 63 71 95 108 141
Myelosuppressive agents	Possible additive hematologic toxicity1 2 3 7 10 11	Use concomitantly with caution; monitor carefully1 3

Ifex/Mesnex Kit Pharmacokinetics

Absorption

Bioavailability

Following IV administration, peak plasma concentrations of the principal alkylating metabolite are reached within 20–30 minutes.¹⁰⁴

Distribution

Extent

Widely distributed throughout the body, including the brain and CSF.^{3 98 99} Distributed into milk.¹

Elimination

Metabolism

Extensively metabolized, principally in the liver, to active and inactive metabolites.^{3 96 104 105}

Metabolized to 4-hydroxyifosfamide (in equilibrium with acyclic tautomer aldoifosfamide),^{1 2 3 96 103 104 105} then to 4-ketoifosfamide.^{1 2 3 96} Also metabolized to chloroacetaldehyde, 2-dechloroethylifosfamide, and 3-dechloroethylifosfamide.^{1 2 3 96 103 104 105}

Aldoifosfamide spontaneously splits into ifosfamide mustard (primary alkylating metabolite) and to acrolein^{1 2 3 96 103} and may be enzymatically metabolized to carboxyifosfamide.^{1 2 3 96}

Elimination Route

Excreted principally in urine.^{1 2 3 96}

Half-life

Terminal half-life averages 4–8 hours in adults.^{3 85 86 104}

Stability

Storage

Parenteral

Powder for Injection

20–25°C;^{1 106 113} protect from temperature >30°C.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible

Dextrose 5% in Ringer’s injection

Dextrose 5% in sodium chloride 0.9%

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Sodium lactate (1/6) M

Drug Compatibility

Admixture CompatibilityHID

Compatible

Carboplatin

Carboplatin with etoposide

Cisplatin

Cisplatin with etoposide

Epirubicin HCl

Etoposide

Fluorouracil

Mesna

Incompatible

Mesna with epirubicin HCl

Y-Site CompatibilityHID

Compatible

Allopurinol sodium

Amifostine

Amphotericin B cholesteryl sulfate complex

Aztreonam

Doxorubicin HCl liposome injection

Etoposide phosphate

Filgrastim

Fludarabine phosphate

Gallium nitrate

Gemcitabine HCl

Granisetron HCl

Lansoprazole

Linezolid

Melphalan HCl

Ondansetron HCl

Oxaliplatin

Paclitaxel

Pemetrexed disodium

Piperacillin sodium–tazobactam sodium

Propofol

Sargramostim

Sodium bicarbonate

Teniposide

Thiotepa

Topotecan HCl

Vinorelbine tartrate

Incompatible

Cefepime HCl

Methotrexate sodium

ActionsActions

• 
  

  Interferes with DNA replication and transcription of RNA, resulting in disruption of nucleic acid function.^{1 2 3 143 144 145 146}

  
  


• 
  

  Also has immunosuppressive activity.^{112 144 146}

  
  

Advice to Patients

• 
  

  Risk of bladder toxicity, myelosuppresion, and neurotoxicity.^a

  
  


• 
  

  Importance of informing clinicians if excessive sleepiness, confusion, or hallucinations occur.^a

  
  


• 
  

  Advise that alopecia is likely.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹ Advise pregnant women of risk to the fetus.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Ifosfamide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Kit	1 g, For injection, for IV infusion, Ifosfamide (Ifex Kit) 100 mg/mL (1 g), Injection, Mesna (Mesnex) (with benzyl alcohol)	Ifex/Mesnex Kit	Bristol-Myers Squibb
		100 mg/mL (1 g), Injection, Ifosfamide 100 mg/mL (1 g) Injection, Mesna (with benzyl alcohol)	Ifosfamide Injection/Mesna Injection Kit	Sicor
		3 g, For injection, for IV infusion, Ifosfamide (Ifex) 100 mg/mL (1 g), Injection, Mesna (Mesnex) (with benzyl alcohol)	Ifex/Mesnex Kit	Bristol-Myers Squibb
		100 mg/mL (3 g), Injection, Ifosfamide 100 mg/mL (1 g) Injection, Mesna (with benzyl alcohol)	Ifosfamide Injection/Mesna Injection Kit	Sicor

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Bristol-Myers Squibb. Ifex (ifosfamide for injection) prescribing information. Princeton, NJ; 1998 Jun.

2. Schoenike SE, Dana WJ. Ifosfamide and mesna. Clin Pharm. 1990; 9:179-91. [IDIS 264394] [PubMed 2107997]

3. Dechant KL, Brogden RN, Pilkington T et al. Ifosfamide/mesna: a review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. Drugs. 1991; 42:428-67. [PubMed 1720382]

4. Loehrer PJ, Lauer R, Roth BJ et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Int Med. 1988; 109:540-6. [IDIS 246234] [PubMed 2844110]

5. Food and Drug Administration. List of orphan product designations & approvals. 1995 Apr.

6. Motzer RJ, Cooper K, Geller NL et al. The role of ifosfamide plus cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors. Cancer. 1990; 66:2476-81. [IDIS 275597] [PubMed 2174300]

7. Ghosn M, Droz JP, Theodore C et al. Salvage chemotherapy in refractory germ cell tumors with etoposide (VP-16) plus ifosfamide plus high-dose cisplatin. Cancer. 1988; 62:24-7. [IDIS 244194] [PubMed 3133101]

8. Hansen HH, Rorth M. Lung cancer. In: Pinedo HM, Longo DL, Chabner BA eds. Cancer chemotherapy and biological response modifiers annual 14. 1993:442-3.

9. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther. 2000; 42:83-92. [PubMed 10994034]

10. Smith IE, Perren TJ, Ashley SA et al. Carboplatin, etoposide, and ifosfamide as intensive chemotherapy for small-cell lung cancer. J Clin Oncol. 1990; 8:899-905. [PubMed 2159056]

11. Thatcher N, Lind M, Stout R et al. Carboplatin, ifosfamide and etoposide with mid-course vincristine and thoracic radiotherapy for ”limited’ stage small cell carcinoma of the bronchus. Br J Cancer. 1989; 60:98-101. [PubMed 2553090]

12. Loehrer PJ, Rynard S, Ansari R et al. Etoposide, ifosfamide, and cisplatin in extensive small cell lung cancer. Cancer. 1992; 69:669-73. [IDIS 291929] [PubMed 1309677]

13. Havemann K, Wolf M, Drings P et al. Experience of a german multicenter study group with ifosfamide in small cell lung cancer. Semin Oncol. 1989; 16:9-18. [PubMed 2539648]

14. Eberhardt W, Niederle N. Ifosfamide in non-small cell lung cancer: a review. Semin Oncol. 1992; 19:40-8. [PubMed 1329211]

15. de Schepper J, Hachimi-Idrissi S, Louis O et al. Bone metabolism and mineralisation after cytotoxic chemotherapy including ifosfamide. Arch Dis Child. 1994; 71:346-8. [IDIS 336803] [PubMed 7979531]

16. Crino L, Scagliotti GV, Ricci S et al. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol. 1999; 17:3522-30. [IDIS 437734] [PubMed 10550150]

17. Cullen MH. Mitomycin, ifosfamide, and cisplatin in non-small cell lung cancer. Oncology. 1993; 50:31-4. [PubMed 8387176]

18. Krämer A, Goldschmidt H, Hahh U. Progressive renal failure in two breast cancer patients after high-dose ifosfamide. Lancet. 1994; 344:1569.

19. Garcia AA. Ifosfamide-induced fanconi syndrome. Ann Pharmacother. 1995; 29:590-1. [IDIS 349730] [PubMed 7663031]

20. Sutton GP, Blessing JA, McGuire WP et al. Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a gynecologic oncology group study. Am J Obstet Gynecol. 1993; 168:805-7. [IDIS 311460] [PubMed 8456884]

21. Coleman RE, Harper PG, Gallagher C et al. A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol. 1986; 18:280-3. [PubMed 3802384]

22. Buxton EJ, Meanwell CA, Hilton C et la. Combination bleomycin, ifosfamide, and cisplatin chemotherapy in cervical cancer. J Natl Cancer Inst. 1989; 81:359-61. [IDIS 251803] [PubMed 2464699]

23. Cervical cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Aug.

24. Sutton GP, Blessing JA, Adcock L et al. Phase II study of ifosfamide and mesna in patients with previously-treated carcinoma of the cervix. Invest New Drugs. 1989; 7:341-3. [PubMed 2513286]

25. Murad AM, Triginelli SA, Ribolta JCL. Phase II trial of bleomycin, ifosfamide, and carboplatin in metastatic cervical cancer. J Clin Oncol. 1994; 12:55-9. [IDIS 324689] [PubMed 7505808]

26. Ovarian epithelial cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Oct.

27. Lorusso V, Catino A, Leone B et al. Carboplatin plus ifosfamide as salvage treatment of epithelial ovarian cancer: a pilot study. J Clin Oncol. 1993; 11:1952-6. [PubMed 8410121]

28. Sutton GP, Blessing JA, Homesley HD et al. Phase II trial of ifosfamide and mesna in advanced ovarian carcinoma: a gynecologic oncology group study. J Clin Oncol. 1989; 7:1672-6. [PubMed 2509641]

29. Markman M, Hakes T, Reichman B et al. Ifosfamide and mesna in previously treated advanced epithelial ovarian cancer: activity in platinum-resistant disease. J Clin Oncol. 1992; 10:243-8. [PubMed 1732425]

30. Uterine sarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sep 1.

31. Sutton GP, Blessing JA, Rosenshein N et al. Phase II trial of ifosfamide and mesna in mixed mesodermal tumors of the uterus (a gynecologic oncology group study). Am J Obstet Gynecol. 1989; 161:309-12. [IDIS 303860] [PubMed 2548382]

32. Sutton GP, Blessing JA, Barrett RJ et al. Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a gynecologic oncology group study. Am J Obstet Gynecol. 1992; 166:556-9. [IDIS 292718] [PubMed 1536229]

33. Ewing’s sarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sep 1.

34. Meyer WH, Kun L, Marina N et al. Ifosfamide plus etoposide in newly diagnosed Ewing’s sarcoma of bone. J Clin Oncol. 1992; 10:1737-42. [PubMed 1403056]

35. Miser JS, Kinsella TJ, Triche TJ et al. Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol. 1987; 5:191-8.

36. Kung FH, Pratt CB, Vega RA et al. Ifosfamide/etoposide combination in the treatment of recurrent malignant solid tumors of childhood. Cancer. 1993; 71:1898-903. [IDIS 310893] [PubMed 8448755]

37. Antman KH. Chemotherapy of advanced sarcomas of bone and soft tissue. Semin Oncol. 1992; 19:13-22. [PubMed 1485169]

38. Jürgens H, Exner U, Khl J et al. High-dose ifosfamide with mesna uroprotection in Ewing’s sarcoma. Cancer Chemother Pharmacol. 1989; 24:40-44S.

39. Demeocq F, Oberlin O, Benz-Lemoine E et al. Initial chemotherapy including ifosfamide in the management of Ewing’s sarcoma: preliminary results a protocol of the French Pediatric Oncology Society (SFOP). Cancer Chemother Pharmacol. 1989; 24:45-47S. [PubMed 2541937]

40. Osteosarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sept 1.

41. Pratt CB. Ifosfamide studies for primary or recurrent pediatric malignant solid tumors and leukemia. Semin Oncol. 1990; 17:31-4. [PubMed 2185546]

42. Marti C, Kroner T, Remagen W et al. High-dose ifosfamide in advanced osteosarcoma. Cancer Treat Rep. 1985; 69:115-7. [IDIS 197201] [PubMed 3855382]

43. Adult soft tissue sarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sept 1.

44. Elias A, Ryan L, Sulkes A et al. Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol. 1989; 7:1208-16. [PubMed 2504890]

45. Antman K, Crowley J, Balcerzak SP et al. An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas. J Clin Oncol. 1993; 11:1276-85. [PubMed 8315425]

46. Antman KH, Ryan L, Elias A et al. Response to ifosfamide and mesna: 124 previously treated patients with metastatic or unresectable sarcoma. J Clin Oncol. 1989; 7:126-31. [PubMed 2491883]

47. Childhood rhabdomyosarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Nov 30.

48. Magrath I, Sandlund J, Raynor A et al. A phase II study of ifosfamide in the treatment of recurrent sarcomas in young people. Cancer Chemother Pharmacol. 1986; 18:25-8S.

49. de Kraker J, Voute PA. Ifosfamide, mesna and vincristine in pediatric oncology. Cancer Treat Rev. 1983; 10:165-6. [PubMed 6414690]

50. Otten J, Flamant F, Rodary C et al. Treatment of rhabdomyosarcoma and other malignant mesenchymal tumours of childhood with ifosfamide + vincristine + dactinomycin (IVA) as front-line therapy (a SIOP study). Cancer Chemother Pharmacol. 1989; 24:30S.

51. Pappo AS, Etcubanas E, Santana VM et al. A phase II trial of ifosfamide in previously untreated children and adolescents with unresectable rhabdomyosarcoma. Cancer. 1993; 71:2119-25. [IDIS 311044] [PubMed 8443761]

52. Testicular Cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Nov 30.

53. Non-small cell lung cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Aug.

54. Small cell lung cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Oct.

55. Cabanillas F. Ifosfamide combinations in lymphoma. Semin Oncol. 1990; 17:58-82. [PubMed 2333524]

56. Adult non-Hodgkin’s lymphoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sept 1.

57. Armitage JO. Treatment of non-hodgkin’s lymphoma. N Engl J Med. 1993; 328:1023-30. [IDIS 312148] [PubMed 8450856]

58. Antman KH, Elias A, Ryan L. Ifosfamide and mesna: response and toxicity at standard- and high-dose schedules. Semin Oncol. 1990; 17: 68-73.

59. Brade WP, Herdich K, Kachel-Fischer U et al. Dosing and side-effects of ifosfamide plus mesna. Cancer Res Clin Oncol. 1991; 117:5164-86.

60. Wilms’ tumor. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Sept 1.

61. Tournade MF, Lemerle J, Brunat-Mentigny M et al. Ifosfamide is an active drug in Wilms’ tumor: a phase II study conducted by the French Society of Pediatric Oncology. J Clin Oncol. 1988; 6:793-6. [PubMed 2835442]

62. Skinner R, Sharkey IA, Pearson ADJ et al. Ifosfamide, mesna, and nephrotoxicity in children. J Clin Oncol. 1993; 11:173-90. [PubMed 8418231]

63. Culine S, Ghosn M, Droz J. Inappropriate antidiuretic hormone secretion induced by ifosfamide. Eur J Cancer. 1990; 26:922. [PubMed 2145942]

64. Rossi R, Gödde A, Kleinbrand A et al. Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced nephrotoxicity: analysis of 120 patients. J Clin Oncol. 1994; 12:159-65. [IDIS 324703] [PubMed 8270973]

65. Husband DJ, Watkin SW. Fatal hypokalemia associated with ifosfamide/mesna chemotherapy. Lancet. 1988; :1116. [IDIS 241449] [PubMed 2896952]

66. Newbury-Ecob RA, Nobel VW, Barbor PRH. Ifosfamide-induced fanconi syndrome. Lancet. 1989; :1328.

67. Rossi R, Kleinebrand A, Gdde A et al. Increased risk of ifosfamide-induced renal Fanconi’s syndrome after unilateral nephrectomy. Lancet. 1993; 341:755. [IDIS 311474] [PubMed 8095648]

68. Burk CD, Restaino I, Kaplan BS et al. Ifosfamide-induced renal tubular dysfunction and rickets in children with Wilms tumor. J Pediatr. 1990; 117:331-5. [IDIS 270956] [PubMed 2166154]

69. Skinner R, Pearson ADJ, Price L et al. Nephrotoxicity after ifosfamide. Arch Dis Childhood. 1990; 65:732-8.

70. Devalck C, Ismaili K, Ferster A. Acute ifosfamide-induced proximal tubular toxic reaction. J Pediatr. 1991; 118:325-6. [IDIS 278160] [PubMed 1993970]

71. Goren MP, Wright RK, Horowitz ME et al. Ifosfamide-induced subclinical tubular nephrotoxicity despite mesna. Cancer Treat Rep. 1987; 71:127-30. [IDIS 228859] [PubMed 2879626]

72. Willemse PHB, de Jong PE, Elema JD et al. Severe renal failure following high-dose ifosfamide and mesna. Cancer Chemother Pharmacol. 1989; 23:329-30. [PubMed 2495864]

73. Pratt CB, Meyer WH, Jenkins JJ et al. Ifosfamide, Fanconi’s syndrome, and rickets. J Clin Oncol. 1991; 9:1495-9. [PubMed 1649270]

74. Beckwith C, Flaharty KK, Cheung AK et al. Fanconi’s syndrome due to ifosfamide. Bone Marrow Transplant. 1989; 11:71-3.

75. Ifosfamide-induced fanconi’s syndrome with growth failure in a 2-year-old child. Am J Pediatr Hematol/Oncol. 1991; 13:39-41.

76. Rossi R, Ehrich JHH. Partial and complete de Toni-Debre-Fanconi syndrome after ifosfamide chemotherapy of childhood malignancy. Eur J Clin Pharmacol. 1993; 44:43-5S.

77. Heney D, Wheeldon J, Rushworth P et al. Progressive renal toxicity due to ifosfamide. Arch Dis Childhood. 1991; 66:966-70.

78. Patterson WP, Khojasteh A. Ifosfamide-induced renal tubular defects. Cancer. 1989; 63:649-51. [IDIS 250525] [PubMed 2914270]