Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administered for 4 consecutive weeks in combination with BCNU administered on the first day of each 6-week cycle. We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU (100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Newly diagnosed patients received up to 3 cycles before radiotherapy, while recurrent patients received up to 8 cycles. The primary end point of this study was radiographic response, while time to progression and overall survival were also assessed. Seventy-six patients were treated, including 37 with newly diagnosed tumors and 39 with recurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade > or =3) included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia (7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosed patients (14%; 95% CI, 5%-29%) achieved a radiographic response (1 complete response and 4 partial responses). Five patients with recurrent MG also achieved a response (1 complete response and 4 partial responses; 13%; 95% CI, 4%-27%). More than 40% of both newly diagnosed and recurrent patients achieved stable disease. Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme patients and 16.9 weeks for recurrent anaplastic astrocytoma/ anaplastic oligodendroglioma patients. We conclude that the activity of BCNU plus CPT-11 for patients with MG appears comparable to that of CPT-11 alone and may be more toxic.
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PMID:Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma. 1513 28

(1) Platinum-based chemotherapy is generally used to treat advanced-stage non small-cell lung cancer (stages III and IV), but has only a modest impact on survival. There is no reference treatment. (2) Gefitinib inhibits the tyrosine kinase activity of the receptor for EGF (epidermal growth factor), which is thought to be involved in tumour growth. It has a temporary licence in France and is used on a named-patient basis, but full marketing authorisation has already been granted in Japan, the United States, and elsewhere. (3) Two double-blind dose-finding studies compared two doses of oral gefitinib monotherapy (250 mg/day and 500 mg/day) in patients in whom at least two lines of chemotherapy had failed. The results were favourable, with a median survival of 6 months and a symptomatic improvement in some patients, but they are undermined by the absence of a placebo group and by major protocol violations. (4) Two double-blind trials, each in more than 1000 patients, showed that gefitinib does not increase the efficacy of first-line platinum combinations. (5) About 15% of patients receiving gefitinib monotherapy in clinical trials stopped taking the treatment because of adverse events. The most frequent were gastrointestinal (diarrhea, nausea, vomiting) and cutaneous (rash, acne, dry skin, pruritus). (6) Interstitial pneumonitis occurred in about 1% of patients, and was fatal in about one-third of cases. (7) Gefitinib is metabolised by the cytochrome P450 isoenzyme CYP3A4, so carries a potentially high risk of interactions. (8) In practice, more thorough assessment of gefitinib is needed to determine whether this new drug is beneficial for patients with non small-cell lung cancer. Marketing authorisation is not currently justified.
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PMID:Gefitinib: new preparation. Non small-cell lung cancer: stricter assessment needed. 1549 96

(1) There is no standard third-line treatment for locally advanced or metastatic non small-cell lung cancer. (2) Erlotinib, like gefitinib, inhibits the tyrosine kinase activity of the epidermal growth factor (EGF) receptor, and has been licensed for sale in the European Union. (3) A double-blind placebo-controlled trial involving 713 patients who had failed to respond to one or two previous chemotherapy regimens showed that erlotinib increased the median survival time by about 2 months (6.7 versus 4.7 months), without improving the quality of this survival. It is not possible to predict precisely which patients are most likely to respond to erlotinib. (4) In first-line treatment, erlotinib was no more effective than placebo as an adjunct to chemotherapy in 2 trials involving 1079 and 1172 patients. (5) The adverse effect profile of erlotinib seems similar to that of gefitinib, mainly consisting of gastrointestinal disturbances (especially diarrhoea: 54% of patients versus 18% on placebo), skin rash (75% versus 17%), and ocular disorders (conjunctivitis: 12% versus 2%). In the comparative trial of second- or third-line treatment, 0.8% of patients developed interstitial pneumonia. (6) Erlotinib, like gefitinib, is metabolized by the cytochrome P450 isoenzyme CYP3A4, potentially creating a high risk of interactions. (7) In practice, the limited benefit of erlotinib seems to be outweighed by its frequent adverse effects. Erlotinib should therefore only be used in clinical trials designed to identify subgroups of patients in whom the risk-benefit balance may be favourable.
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PMID:Erlotinib: new drug. Non small-cell lung cancer: like gefitinib, no established advantage. 1676 93