TAXOTERE in combination with cisplatin and fluorouracil in gastric cancer or head and neck cancer
Patients treated with TAXOTERE in combination with cisplatin and fluorouracil must receive antiemetics and appropriate hydration according to current institutional guidelines. In both studies, G-CSF was recommended during the second and/or subsequent cycles in case of febrile neutropenia, or documented infection with neutropenia, or neutropenia lasting more than 7 days. If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the TAXOTERE dose should be reduced from 75 to 60 mg/m2. If subsequent episodes of complicated neutropenia occur the TAXOTERE dose should be reduced from 60 to 45 mg/m2. In case of Grade 4 thrombocytopenia the TAXOTERE dose should be reduced from 75 to 60 mg/m2. Patients should not be retreated with subsequent cycles of TAXOTERE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover to a level >100,000 cells/mm3. Discontinue treatment if these toxicities persist. [see Warnings and Precautions (5) ].
Recommended dose modifications for toxicities in patients treated with TAXOTERE in combination with cisplatin and fluorouracil are shown in Table 1.
Table 1 - Recommended Dose Modifications for Toxicities in Patients Treated with TAXOTERE in Combination with Cisplatin and Fluorouracil
|Diarrhea grade 3||First episode: reduce fluorouracil dose by 20%.|
Second episode: then reduce TAXOTERE dose by 20%.
|Diarrhea grade 4||First episode: reduce TAXOTERE and fluorouracil doses by 20%.|
Second episode: discontinue treatment.
|Stomatitis/mucositis grade 3||First episode: reduce fluorouracil dose by 20%.|
Second episode: stop fluorouracil only, at all subsequent cycles.
Third episode: reduce TAXOTERE dose by 20%.
|Stomatitis/mucositis grade 4||First episode: stop fluorouracil only, at all subsequent cycles.|
Second episode: reduce TAXOTERE dose by 20%.
In case of AST/ALT >2.5 to ≤5 × UNL and AP ≤2.5× UNL, or AST/ALT >1.5 to ≤5 × UNL and AP >2.5 to≤5 × UNL, TAXOTERE should be reduced by 20%.
In case of AST/ALT >5 × UNL and/or AP >5 × UNL TAXOTERE should be stopped.
The dose modifications for cisplatin and fluorouracil in the gastric cancer study are provided below:
Cisplatin dose modifications and delays
Peripheral neuropathy: A neurological examination should be performed before entry into the study, and then at least every 2 cycles and at the end of treatment. In the case of neurological signs or symptoms, more frequent examinations should be performed and the following dose modifications can be made according to NCIC-CTC grade:
• Grade 2: Reduce cisplatin dose by 20%.
• Grade 3: Discontinue treatment.
Ototoxicity: In the case of grade 3 toxicity, discontinue treatment.
Nephrotoxicity: In the event of a rise in serum creatinine ≥grade 2 (>1.5 × normal value) despite adequate rehydration, CrCl should be determined before each subsequent cycle and the following dose reductions should be considered (see Table 2).
For other cisplatin dosage adjustments, also refer to the manufacturers' prescribing information.
Table 2 – Dose Reductions for Evaluation of Creatinine Clearance
| Creatinine clearance result before next cycle||Cisplatin dose next cycle|
|CrCl = Creatinine clearance|
|CrCl ≥60 mL/min||Full dose of cisplatin was given. CrCl was to be repeated before each treatment cycle.|
|Dose of cisplatin was reduced by 50% at subsequent cycle. If CrCl was >60 mL/min at end of cycle, full cisplatin dose was reinstituted at the next cycle.|
|CrCl between 40 and 59 mL/min|
|If no recovery was observed, then cisplatin was omitted from the next treatment cycle.|
|Dose of cisplatin was omitted in that treatment cycle only. |
|If CrCl was still <40 mL/min at the end of cycle, cisplatin was discontinued.|
|CrCl <40 mL/min|
|If CrCl was >40 and <60 mL/min at end of cycle, a 50% cisplatin dose was given at the next cycle.|
|If CrCl was >60 mL/min at end of cycle, full cisplatin dose was given at next cycle.|
Fluorouracil dose modifications and treatment delays
For diarrhea and stomatitis, see Table 1.
In the event of grade 2 or greater plantar-palmar toxicity, fluorouracil should be stopped until recovery. The fluorouracil dosage should be reduced by 20%.
For other greater than grade 3 toxicities, except alopecia and anemia, chemotherapy should be delayed (for a maximum of 2 weeks from the planned date of infusion) until resolution to grade ≤1 and then recommenced, if medically appropriate.
For other fluorouracil dosage adjustments, also refer to the manufacturers' prescribing information.
TAXOTERE is a cytotoxic anticancer drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing TAXOTERE solutions. The use of gloves is recommended. Please refer to Handling and Disposal .
If TAXOTERE Injection Concentrate, initial diluted solution, or final dilution for intravenous infusion should come into contact with the skin, immediately and thoroughly wash with soap and water. If TAXOTERE Injection Concentrate, initialdiluted solution, or final dilution for intravenous infusion should come into contact with mucosa, immediately and thoroughly wash with water.
Contact of the TAXOTERE concentrate with plasticized PVC equipment or devices used to prepare solutions for infusion is not recommended. In order to minimize patient exposure to the plasticizer DEHP (di-2-ethylhexyl phthalate), which may be leached from PVC infusion bags or sets, the final TAXOTERE dilution for infusion should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.
TAXOTERE Injection Concentrate requires two dilutions prior to administration. Please follow the preparation instructions provided below. Note: Both the TAXOTERE Injection Concentrate and the diluent vials contain an overfill to compensate for liquid loss during preparation. This overfill ensures that after dilution with the entire contents of the accompanying diluent, there is an initial diluted solution containing 10 mg/mL docetaxel.
The table below provides the fill range of the diluent, the approximate extractable volume of diluent when the entire contents of the diluent vial are withdrawn, and the concentration of the initial diluted solution for TAXOTERE 20 mg and TAXOTERE 80 mg (see Table 3).
Table 3 – Initial Dilution of TAXOTERE Injection Concentrate
|Product||Diluent 13% (w/w) ethanol in water for injection|
|Approximate extractable volume of diluent when entire contents are withdrawn|
|Concentration of the initial diluted solution|
20 mg/0.5 mL
|1.88 – 2.08 mL||1.8 mL||10 mg/mL|
80 mg/2 mL
|6.96 – 7.70 mL||7.1 mL||10 mg/mL|
Preparation and Administration
A.Initial Diluted Solution
- TAXOTERE vials should be stored between 2 and 25°C (36 and 77°F). If the vials are stored under refrigeration, allow the appropriate number of vials of TAXOTERE Injection Concentrate and diluent (13% ethanol in water for injection) vials to stand at room temperature for approximately 5 minutes.
- Aseptically withdraw the entire contents of the appropriate diluent vial (approximately 1.8 mL for TAXOTERE 20 mg and approximately 7.1 mL for TAXOTERE 80 mg) into a syringe by partially inverting the vial, and transfer it to the appropriate vial of TAXOTERE Injection Concentrate. If the procedure is followed as described, an initial diluted solution of 10 mg docetaxel/mL will result.
- Mix the initial diluted solution by repeated inversions for at least 45 seconds to assure full mixture of the concentrate and diluent. Do not shake.
- The initial diluted TAXOTERE solution (10 mg docetaxel/mL) should be clear; however, there may be some foam on top of the solution due to the polysorbate 80. Allow the solution to stand for a few minutes to allow any foam to dissipate. It is not required that all foam dissipate prior to continuing the preparation process.
The initial diluted solution may be used immediately or stored either in the refrigerator or at room temperature for a maximum of 8 hours.
B.Final Dilution for Infusion
- Aseptically withdraw the required amount of initial diluted TAXOTERE solution (10 mg docetaxel/mL) with a calibrated syringe and inject into a 250 mL infusion bag or bottle of either 0.9% Sodium Chloride solution or 5% Dextrose solution to produce a final concentration of 0.3 to 0.74 mg/mL.
If a dose greater than 200 mg of TAXOTERE is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/mL TAXOTERE is not exceeded.
- Thoroughly mix the infusion by manual rotation.
- As with all parenteral products, TAXOTERE should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the TAXOTERE initial diluted solution or final dilution for intravenous infusion is not clear or appears to have precipitation, these should be discarded.
The final TAXOTERE dilution for infusion should be administered intravenously as a 1-hour infusion under ambient room temperature and lighting conditions.
TAXOTERE infusion solution, if stored between 2 and 25°C (36 and 77°F) is stable for 4 hours. Fully prepared TAXOTERE infusion solution (in either 0.9% Sodium Chloride solution or 5% Dextrose solution) should be used within 4 hours (including the 1 hour i.v. administration).
DOSAGE FORMS AND STRENGTHS
TAXOTERE 80 mg/2 mL
TAXOTERE (docetaxel) Injection Concentrate 80 mg/2 mL: 80 mg docetaxel in 2 mL polysorbate 80 and Diluent for TAXOTERE 80 mg (13% (w/w) ethanol in water for injection). Both items are in a blister pack in one carton.
TAXOTERE 20 mg/0.5 mL
TAXOTERE (docetaxel) Injection Concentrate 20 mg/0.5 mL: 20 mg docetaxel in 0.5 mL polysorbate 80 and Diluent for TAXOTERE 20 mg (13% (w/w) ethanol in water for injection). Both items are in a blister pack in one carton.