An Open, Prospective, Multicenter Study of Trimetrexate With Leucovorin Rescue for AIDS Patients With Pneumocystis Carinii Pneumonia (PCP) and Serious Intolerance to Approved Therapies

Inclusion Criteria Concurrent Medication: Allowed: Noninvestigational therapies as needed. Maintenance therapy with investigational triazoles such as itraconazole and SCH 39304. High-dose corticosteroids (exceed physiologic replacement doses) including oral prednisone 40 mg bid for 5 days, 40 mg daily for 5 days and then 20 mg daily for the remainder of PCP therapy. Same dose for methylprednisolone. Concurrent Treatment: Allowed: Any ventilatory support, antihypertensive agents, invasive monitoring, and other necessary medical intervention, according to his/her medical status, personal wishes, and the judgment of his/her physician. Patients must have: HIV seropositivity. Diagnosis of Pneumocystis carinii pneumonia (PCP). Serious intolerance to trimethoprim / sulfamethoxazole (TMP / SMX) therapy defined as follows: Platelets < 50000 platelets/mm3. Neutrophil count (polys plus bands) = or < 500 cells/mm3 on at least two occasions = or > 12 hours apart. Mucocutaneous reaction - blistering rash, mucosal involvement, generalized maculopapular eruption, or intolerable pruritus. Hepatitis demonstrated by transaminase elevation > 5 times the upper limit of normal, or = or > 300 IU if baseline is abnormal. Drug fever with daily temperature = or > 103 degrees F beginning after the 5th day of treatment persisting for at least 3 days and not responsive to antipyretic therapy, with no other discernible cause. Any other severe or life-threatening adverse reaction to TMP / SMX which, in the investigator's opinion, makes continued or recurrent treatment with TMP / SMX inadvisable as determined on a case-by-case basis. Serious intolerance to pentamidine therapy defined as follows: Platelets < 50000 platelets/mm3. Neutrophil count (polys plus bands) = or < 500 cells/mm3 on at least two occasions = or > 12 hours apart. Serum creatinine > 3.0 mg/dl. Systolic blood pressure < 90 mm requiring supportive therapy. Symptomatic hypoglycemia with blood glucose < 40, or hyperglycemia requiring therapy. Pancreatitis with laboratory confirmation (abnormal amylase and/or lipase). Any other severe or life-threatening adverse reaction to pentamidine, which, in the investigator's opinion, makes continued or recurrent treatment with pentamidine inadvisable as determined on a case-by-case basis. Informed consent by patient or legal guardian. Prior Medication: Required: Trimethoprim / sulfamethoxazole and pentamidine therapies. Prior Medication: Allowed: Myelosuppressive or nephrotoxic agents including zidovudine. History of high-risk behavior for HIV infection - homosexual or bisexual men, intravenous drug abusers, recipients of HIV-infected blood products, or sexual partners of persons in these groups may be admitted without proof of HIV infection. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate. Patients with a less severe adverse reaction may be enrolled if, in the opinion of the investigator, these adverse effects do not prohibit rechallenge with the drug. Concurrent Medication: Excluded: Myelosuppressive or nephrotoxic agents including zidovudine and ganciclovir. Investigational therapies. Patients with the following are excluded: History of Type I hypersensitivity (i.e., urticaria, angioedema, or anaphylaxis), exfoliative dermatitis, or other life-threatening reactions due to trimetrexate. Patients with a less severe adverse reaction may be enrolled if, in the opinion of the investigator, these adverse effects do not prohibit rechallenge with the drug.