Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Taxanes have been shown to interact with anti-apoptotic proteins. In the present study we investigated whether the addition of taxane in combination with DNA damaging drugs can further enhance tumor shrinkage in cases with incomplete response to radiotherapy. Since the dose of docetaxel in combination with carboplatin is not known, the above hypothesis was tested in the context of a dose escalation phase I study. Twenty-eight patients with locally advanced chest or pelvic tumors, showing residual disease on CT scans performed 40 d following docetaxel radio-chemotherapy, were recruited in a dose escalation protocol of docetaxel/carboplatin supported with amifostine and GM-CSF. The starting dose of docetaxel was 40 mg/m2 every 2 weeks. Carboplatin dose was calculated using the Calvert formula and was escalated in cohorts of 4 patients (starting dose AUC2 every two weeks; AUC0.5 increments up to AUC3). Thereafter the docetaxel dose was increased to 50 and 60 mg/m2, while carboplatin was escalated (by AUC0.5 increments) starting from AUC3 and AUC4 respectively. Amifostine (600 mg/m2) was administered i.v. before carboplatin and GM-CSF (480 microg) was injected s.c. on days 5, 6 and 10, 11 of each cycle. Six cycles were given and response was assessed 2 weeks after the end of chemotherapy. None out of four patients treated in the 6th dose level cohort (50 mg/m2 of docetaxel and AUC4 of carboplatin every 2 weeks) showed any grade 2-4 hematologic toxicity. Mild non-hematologic toxicity such as neuropathy, leg edema, pleural effusion, pyrexia, alopecia grade 2 and hypersensitivity was observed in 4-12% of patients. Out of four patients treated in a 7th cohort (docetaxel 60 mg/m2 and carboplatin AUC4), one developed grade IV neutropenia and two developed grade 3 severe asthenia requiring treatment delay for 2 weeks. Out of 11 patients with PR following docetaxel radio-chemotherapy, 7 (63%) showed CR after docetaxel/carboplatin additional chemotherapy. Eight out of 17 patients with MR following docetaxel radio-chemotherapy showed PR (47%) and one showed CR (6%) after additional chemotherapy. High dose combined docetaxel (50 mg/m2) and carboplatin (AUC4) chemotherapy can be safely administered on a two-weekly basis if supported with amifostine and GM-CSF. Such an additional therapy may be important in patients with incomplete response after chemo-RT. Broad spectrum cytoprotection with amifostine and GM-CSF may also contribute to the reduction of incidence of neurosensory reactions and asthenia in patients treated with taxanes.
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PMID:Phase I/II dose escalation study of docetaxel and carboplatin combination supported with amifostine and GM-CSF in patients with incomplete response following docetaxel chemo-radiotherapy: additional chemotherapy enhances regression of residual cancer. 1087 20

We report a case with unexpected toxicity after low-dose docetaxel chemotherapy. The patient had a history of clinically latent HCV-positive hepatic cirrhosis when she presented with inoperable pulmonary adenocarcinoma. She was recruited in a protocol combining standard radiotherapy (RT) with docetaxel (30 mg/m2 week). On day 7, after the 1st docetaxel infusion, grade III neutropenia (980 neutrophils), grade II platelet toxicity (90,000/ml) and lymphopenia (486/ml) had developed. Chemotherapy and RT were interrupted and the neutrophil counts were partially restored (1400/ml), while the platelet counts were back to normal (140,000/ml) and the lymphocyte counts were further reduced (320/ml), on day 15. Bilateral leg oedema and hair loss appreared. On day 21, there was a full restoration of neutrophil counts (1890/ml), while there was persistent lymphocytopenia (300/ml). Alopecia grade III was now evident. Dysphagia grade II complicated with fungal oropharyngeal infection appeared on day 24 (24 Gy of RT). One more dose of docetaxel of 30 mg/m2 was given on day 36 Grade II neutropenia (1050/ml) and grade III platelet toxicity (48,000/ml) were observed 14 days after the second docetaxel dose, while dysphagia grade II appeared once again. After a one-week delay, RT was continued to a total dose of 54 Gy. Liver function tests remained unchanged throughout the treatment. Post-RT CT-scan of the chest and upper abdomen showed complete response of the lung lesion. We suggest that, when docetaxel is chosen to treat cancer patients with HCV-positive hepatic cirrhosis, a starting dose schedule reduced by at least 50% should be considered before escalating to the standard dose.
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PMID:Unexpected toxicity after low-dose docetaxel treatment of a cancer patient with clinically latent HCV-positive hepatic cirrhosis. 1217 50