Interstitial pneumonitis associated with ifosfamide therapy

Article Abstract:

Ifosfamide and cyclophosphamide are closely related chemotherapeutic agents. Both are transformed into active alkylating agents by liver enzymes, and both compounds are degraded to form acrolein and chloroacetaldehyde. These two compounds are believed to account for some of the drugs' unwanted toxic effects. Since the toxic by-products are the same, it is not surprising that many of the toxic effects of ifosfamide and cyclophosphamide are similar as well. These include nausea, bone marrow suppression, hemorrhagic cystitis, and dysfunction of the gonads. With higher doses, an antidiuretic effect can occur, leading to low sodium, loss of hair, and damage to the heart muscle. However, although previous reports have associated cyclophosphamide with interstitial pneumonitis, an inflammation of the lungs, there have been no reports of a similar condition resulting from ifosfamide treatment. Now, however, the case of a 58-year-old woman illustrates that interstitial pneumonitis can be a complication of ifosfamide treatment, as well. The woman had developed chest pain and the presence of a poorly differentiated sarcoma was identified by removal a portion of the lung. She was given radiation treatment and was well for almost a year until scattered metastases appeared. The patient was placed on a combined chemotherapeutic regimen consisting of doxorubicin, dacarbazine, mesna, and ifosfamide. After the fifth cycle of chemotherapy the patient developed symptoms of interstitial pneumonitis. The patient was treated with prednisone, and improved temporarily, but ultimately her condition deteriorated and she died. Autopsy confirmed the diagnosis of interstitial pneumonitis. Now that ifosfamide is commercially available, physicians should be aware of the possibility of interstitial pneumonitis as a potential complication. (Consumer Summary produced by Reliance Medical Information, Inc.)

Diagnosis, Causes of, Pulmonary fibrosis, Cyclophosphamide

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Phase II study of doxorubicin plus ifosfamide/mesna in patients with advanced breast cancer

Article Abstract:

Effective cancer chemotherapy must balance the destruction of cancer cells against the destruction of normal cells, and therapeutic dosed are usually limited by toxic side effects. Ifosfamide is a member of a class of chemical compounds called alkylating agents, which indiscriminately attach alkyl groups to chemically reactive sites within the cell. The DNA of cancer cells is especially reactive, which accounts for the drug's antitumor activity, but its wide spectrum of chemical reactivity almost always results in toxic side effects. However, it has been found that the addition of mesna, a thiol-containing compound, provides some protection against the side effects of ifosfamide, allowing higher and more effective doses to be used. Doxorubicin is currently the most effective single drug against breast cancer, but some cancers still can develop resistance to this agent. The combination of doxorubicin, ifosfamide, and mesna was used in the treatment of 31 breast cancer patients with a poor prognosis. In this study, poor prognosis included either metastatic spread to the viscera or inflammatory recurrences; nine patients previously failed to respond to mitoxantrone. Five patients had complete responses to the doxorubicin-ifosfamide-mesna protocol; 17 had partial responses. The overall response rate was 71 percent; among the patients unresponsive to mitoxantrone therapy 67 percent improved with the combination therapy. Since the combination therapy was administered, 82 percent of the responding patients have relapsed and 65 percent have died; the median survival period was 44 weeks. The relatively high response rate among these poor prognosis patients indicates a high antitumor activity of the regimen and suggests that further investigation of the combination is in order. (Consumer Summary produced by Reliance Medical Information, Inc.)

Breast cancer, Doxorubicin

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Ifosfamide is an inactive substance in the treatment of pancreatic carcinoma

Article Abstract:

In the United States, carcinoma of the pancreas is the fourth most common cause of death from cancer. Anti-cancer drugs have not been effective in the treatment of advanced inoperable pancreatic cancer. Reported response rates of the Gastrointestinal Tumor Study Group (GITSG) for single and multiple drug treatments range between 15 to 19 percent with median survival time of approximately 12 weeks. There have been reports of some success in treatment of pancreatic cancer with alkylating agents, such as ifosfamide. Ifosfamide can be toxic, causing bleeding and inflammation in the urinary tract. This can be prevented with the use of reducing agents such as N-acetylcysteine or mesna. The treatment of 30 patients with advanced inoperable pancreatic cancer with ifosfamide and mesna was investigated by the GITSG. Partial responses, measured by a 50 percent reduction of the tumors, were reported in three patients (10 percent) and the median survival time was just 11 weeks. Five of the patients had blood in their urine, which was indicative of toxicity to the urinary tract, but the major toxic effect of the drug therapy was neurological. Twelve of the patients (41 percent) suffered at least one episode of neurologic toxicity. Six of the patients suffered mild or moderate neurologic episodes such as numbness, problems walking and tiredness. Four of the patients had severe neurologic problems such as confusion, seizures, and hallucinations; two died from the therapy, one from a cerebral infarction. Treatment of pancreatic cancer with ifosfamide and mesna for protection of the urinary system was not successful. (Consumer Summary produced by Reliance Medical Information, Inc.)

Pancreatic cancer, Alkylating agents

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