Newtaxel-A Special Precautions

Toxic Death: Breast Cancer: Docetaxel administered at 100 mg/m² was associated with deaths considered possibly or probably related to treatment in 2.0% (19/965) of metastatic breast cancer patients, both previously treated and untreated, with normal baseline liver function and in 11.5% (7/61) of patients with various tumor types who had abnormal baseline liver function (ALT and AST >1.5 times ULN together with ALP >2.5 times ULN). Among patients dosed at 60 mg/m², mortality related to treatment occurred in 0.6% (3/481) of patients with normal liver function, and in 3 of 7 patients with abnormal liver function. Approximately half of these deaths occurred during the first cycle. Sepsis accounted for the majority of the deaths.
Non-Small Cell Lung Cancer: Docetaxel administered at a dose of 100 mg/m² in patients with locally advanced or metastatic non-small cell lung cancer who had a history of prior platinum based chemotherapy was associated with increased treatment-related mortality (14% and 5% in two randomized, controlled studies). There were 2.8% treatment-related deaths among the 176 patients treated at the 75 mg/m² dose in the randomized trials. Among patients who experienced treatment-related mortality at the 75 mg/m² dose level, 3 of 5 patients had a PS of 2 at study entry.
Used in Pregnancy & Lactation: Docetaxel can cause fetal harm when administered to pregnant women. Studies in both rats and rabbits at doses ≥0.3 and 0.03 mg/kg/day, respectively (about 1/50 and 1/300 the daily maximum recommended human dose on a mg/m2 basis), administered during the period of organogenesis, have shown that Docetaxel is embryotoxic and fetotoxic (characterized by intrauterine mortality, increased resorption, reduced fetal weight, and fetal ossification delay). The doses indicated above also caused maternal toxicity. There are no adequate and well-controlled studies in pregnant women using Docetaxel. If Docetaxel is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus or potential risk for loss of the pregnancy. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Docetaxel.
It is not known whether Docetaxel is excreted in human milk. Because many drugs are excreted inhuman milk, and because of the potential for serious adverse reactions in nursing infants from Docetaxel, a decision should be made whether to discontinue nursing or to discontinue the drug,taking into account the importance of the drug to the mother.
Use in Children: The safety and effectiveness of Docetaxel in pediatric patients have not been established.
Use in Elderly: In a study conducted in chemotherapy-naïve patients with NSCLC (TAX326), 148 patients (36%) in the Docetaxel + cisplatin group were 65 years of age or greater. Patients treated with Docetaxel + cisplatin who were 65 years of age or greater were more likely to experience diarrhea (55%), infections (42%), peripheral edema (39%) and stomatitis (28%) compared to patients less than the age of 65 administered the same treatment (43%, 31%, 31% and 21%, respectively).
When Docetaxel was combined with carboplatin for the treatment of chemotherapy-naïve, advanced non-small cell lung carcinoma, patients 65 years of age or greater experienced higher frequency of infection compared to similar patients treated with Docetaxel + cisplatin, and a higher frequency of diarrhea, infection and peripheral edema than elderly patients treated with vinorelbine + cisplatin.
Of the 333 patients treated with Docetaxel every three weeks plus prednisone in the prostate cancer study (TAX327), 209 patients were 65 years of age or greater and 68 patients were older than 75 years. In patients treated with Docetaxel every three weeks, the following TEAEs occurred at rates ≥10% higher in patients 65 years of age or greater compared to younger patients: anemia (71% vs. 56%), infection (37% vs. 24%), nail changes (34% vs. 23%), anorexia (21% vs. 10%), weight loss (15% vs. 4%) respectively.
Among the 221 patients treated with Docetaxel in combination with cisplatin and 5-fluorouracil in the gastric cancer study, 54 were 65 years of age or older and 2 patients were older than 75 years. In this study, the number of patients who were 65 years of age or older was insufficient to determine whether they respond differently from younger patients. However, the incidence of serious adverse reactions was higher in the elderly patients compared to younger patients. The incidence of the following adverse reactions (all grades, regardless of relationship): lethargy, stomatitis, diarrhea, dizziness, edema, febrile neutropenia/neutropenic infection occurred at rates >10% higher in patients who were 65 years of age or older compared to younger patients. Elderly patients treated with TCF should be closely monitored.
Among the 174 and 251 patients who received the induction treatment with NEWTAXEL-A in combination with cisplatin and 5-fluorouracil (TPF) for SCCHN in the TAX323 and TAX324 studies, 18 (10%) and 32 (13%) of the patients were 65 years of age or older, respectively.