Administration of Teotaxol® should be in a facility equipped under the supervision of qualified physician to manage possible complications (e.g., anaphylaxis). Teotaxol® administration is intravenously (IV) over one-hour every 3 weeks. For all indications, dose adjustment due to toxicities should be considered as needed.
- Dosage:
- Breast Cancer
- For locally advanced or metastatic breast cancer after failure of prior chemotherapy, the recommended dose of Teotaxol® is 60 mg/m2 to 100 mg/m2 administered intravenously over 1 hour every 3 weeks.
- For the adjuvant treatment of operable node-positive breast cancer, the recommended Teotaxol® dose is 75 mg/m2 administered 1 hour after doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 every 3 weeks for 6 courses. Prophylactic G-CSF may be used to mitigate the risk of hematological toxicities.
- In combination with trastuzumab the recommended dose of Teotaxol® is 100 mg/m every three weeks, with trastuzumab administered weekly.
- In combination with capecitabine, the recommended dose of Teotaxol® is 75 mg/m every three weeks, with capecitabine administered for 2 weeks followed by a 1week rest period.
- Non-Small Cell Lung Cancer
- For chemotherapy-naïve patients, Teotaxol® was evaluated in combination with cisplatin. The recommended dose of Teotaxol® is 75 mg/m2 administered intravenously over 1 hour immediately followed by cisplatin 75 mg/m2 over 30-60 minutes every 3 weeks.
- For treatment after failure of prior platinum-based chemotherapy, Teotaxol® was evaluated as monotherapy, and the recommended dose is 75 mg/m2 administered intravenously over 1 hour every 3 weeks. A dose of 100 mg/m2 in patients previously treated with chemotherapy was associated with increased hematologic toxicity, infection, and treatment-related mortality in randomized, controlled trials.
- Prostate cancer
- For Metastatic hormonesensitive prostate cancer, the recommended dose of Teotaxol® is 75 mg/m2 every 3 weeks as a 1-hour intravenous infusion for 6 cycles. Prednisone 5 mg orally twice daily is administered continuously.
- For Metastatic castrationresistant prostate cancer, the recommended dose of Teotaxol® is 75 mg/m2. Prednisone 5 mg orally twice daily is administered continuously.
- Gastric adenocarcinoma
- For gastric adenocarcinoma, the recommended dose of Teotaxol® is 75 mg/m2 as a 1-hour intravenous infusion, followed by cisplatin 75 mg/m2, as a 1 to 3 hour intravenous infusion (both on day 1 only), followed by fluorouracil 750 mg/m2 per day given as a 24-hour continuous intravenous infusion for 5 days, starting at the end of the cisplatin infusion. Treatment is repeated every three weeks. Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration.
- Head and Neck Cancer
Patients must receive premedication with antiemetics, and appropriate hydration (prior to and after cisplatin administration). Prophylaxis for neutropenic infections should be administered. All patients treated on the docetaxel containing arms of the TAX323 and TAX324 studies received prophylactic antibiotics.
- In Induction chemotherapy followed by radiotherapy (TAX323), For the induction treatment of locally advanced inoperable SCCHN, the recommended dose of Teotaxol® is 75 mg/m2 as a 1 hour intravenous infusion followed by cisplatin 75 mg/m2 intravenously over 1 hour, on day one, followed by fluorouracil as a continuous intravenous infusion at 750 mg/m2 per day for five days. This regimen is administered every 3 weeks for 4 cycles. Following chemotherapy, patients should receive radiotherapy.
- In Induction chemotherapy followed by chemoradiotherapy (TAX324), For the induction treatment of patients with locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN, the recommended dose of Teotaxol® is 75 mg/m2 as a 1 hour intravenous infusion on day 1, followed by cisplatin 100 mg/m2 administered as a 30-minute to 3 hour infusion, followed by fluorouracil 1000 mg/m2/day as a continuous infusion from day 1 to day 4. This regimen is administered every 3 weeks for 3 cycles. Following chemotherapy, patients should receive chemoradiotherapy.
- Premedication Regimen
All patients should be premedicated with oral corticosteroids (see below for prostate cancer) such as dexamethasone 16 mg per day (e.g., 8 mg twice daily) for 3 days starting 1 day prior to Teotaxol® administration in order to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions.
For hormone-refractory metastatic prostate cancer, given the concurrent use of prednisone, the recommended premedication regimen is oral dexamethasone 8 mg, at 12 hours, 3 hours and 1 hour before the Teotaxol® infusion.
- Dose Adjustment during treatment:
Teotaxol® should be administered when the neutrophil count is ≥ 1,500 cells/mm3. In patients who experienced either febrile neutropenia, neutrophil count < 500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions or severe peripheral neuropathy during Teotaxol® therapy, the dose of Teotaxol® should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 to 60 mg/m2. If the patient continues to experience these reactions at 60 mg/m2, the treatment should be discontinued. Conversely, patients who are dosed initially at 60 mg/m2 and who do not experience febrile neutropenia, neutrophils <500 cells/mm3 for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during Teotaxol® therapy may tolerate higher doses. Patients who develop ≥grade 3 peripheral neuropathy should have Teotaxol® treatment discontinued entirely.
Teotaxol® in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is ≥1,500 cells/mm3. Patients who experience febrile neutropenia should receive G-CSF in all subsequent cycles. Patients who continue to experience this reaction should remain on G-CSF and have their Teotaxol® dose reduced to 60 mg/m2. Patients who experience grade 3 or 4 stomatitis should have their Teotaxol® dose decreased to 60 mg/m2. Patients who experience severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during Teotaxol® therapy should have their dosage of Teotaxol® reduced from 75 to 60 mg/m2. If the patient continues to experience these reactions at 60 mg/m2, treatment should be discontinued.
- Non-Small Cell Lung Cancer
- For monotherapy with Teotaxol® treatment after failure of prior platinum-based chemotherapy, patients who are dosed initially at 75 mg/m2 and who experience either febrile neutropenia, neutrophils<500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions, or other grade 3/4 non-hematological toxicities during Teotaxol® treatment should have treatment withheld until resolution of the toxicity and then resumed at 55 mg/m2. Patients who develop ≥grade 3 peripheral neuropathy should have Teotaxol® treatment discontinued entirely.
- For combination therapy with Teotaxol® for chemotherapy-naïve NSCLC, in patients who are dosed initially at Teotaxol® 75 mg/m2 in combination with cisplatin, and whose nadir of platelet count during the previous course of therapy is <25,000 cells/mm3, in patients who experience febrile neutropenia, and in patients with serious non-hematologic toxicities, the Teotaxol® dosage in subsequent cycles should be reduced to 65 mg/m2. In patients who require a further dose reduction, a dose of 50 mg/m2 is recommended. For cisplatin dosage adjustments, see manufacturers’ prescribing information.
- Prostate Cancer
- For combination therapy with Teotaxol® for hormone-refractory metastatic prostate cancer, Teotaxol® should be administered when the neutrophil count is ≥1,500 cells/mm3. Patients who experience either febrile neutropenia, neutrophils< 500cells/mm3 for more than one week, severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms during Teotaxol® therapy should have the dosage of Teotaxol® reduced from 75 to 60 mg/m2. If the patient continues to experience these reactions at 60 mg/m2, the treatment should be discontinued.
- Gastric or Head and Neck Cancer
- For Teotaxol® in combination with cisplatin and fluorouracil in gastric cancer or head and neck cancer, Patients treated with Teotaxol® 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 Teotaxol® dose should be reduced from 75 mg/m2 to 60 mg/m2. If subsequent episodes of complicated neutropenia occur the Teotaxol® dose should be reduced from 60 mg/m2 to 45 mg/m2. In case of grade 4 thrombocytopenia the Teotaxol® dose should be reduced from 75 mg/m2 to 60 mg/m2. Patients should not be retreated with subsequent cycles of Teotaxol® 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.
- Recommended dose modifications for toxicities in patients treated with Teotaxol® in combination with cisplatin and fluorouracil are shown in Table 1.
Table 1- Recommended Dose Modifications for Toxicities in Patients Treated with Teotaxol® in Combination with Cisplatin and Fluorouracil
Toxicity | Dosage Adjustment |
Diarrhea grade 3 | First episode: reduce fluorouracil dose by 20%. Second episode: then reduce Teotaxol® dose by 20%. |
Diarrhea grade 4 | First episode: reduce Teotaxol® 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 Teotaxol® dose by 20%. |
Stomatitis/mucositis grade 4 | First episode: stop fluorouracil only, at all subsequent cycles. Second episode: reduce Teotaxol® dose by 20%. |
In case of AST/ALT >2.5 to ≤5 x ULN and AP ≤2.5 x ULN, or AST/ALT >1.5 to ≤5 x ULN and AP >2.5 to ≤5 x ULN, Teotaxol® should be reduced by 20%.
In case of AST/ALT >5 x ULN and/or AP >5 x ULN Teotaxol® 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 x normal value)
despite adequate rehydration, CrCl should be determined before each subsequent cycle and
the following dose reductions should be considered (see Table 2).
Table 2 – Dose Reductions for Evaluation of Creatinine Clearance
Creatinine clearance result
before next cycle | Cisplatin dose next cycle |
CrCl ≥60 mL/min | Full dose of cisplatin was given. CrCl was to be repeated
before each treatment cycle. |
CrCl between 40 and 59
mL/min | 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.
If no recovery was observed, then cisplatin was omitted
from the next treatment cycle. |
CrCl <40 mL/min | 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.
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 |
CrCl = Creatinine clearance
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.
- Combination Therapy with Strong CYP3A4 inhibitors:
Avoid using concomitant strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole). There are no clinical data with a dose adjustment in patients receiving strong CYP3A4 inhibitors. Based on extrapolation from a pharmacokinetic study with ketoconazole in 7 patients, consider a 50% Teotaxol® dose reduction if patients require co- administration of a strong CYP3A4 inhibitor.
- Administration Precautions:
Teotaxol® is a cytotoxic anticancer drug and, as with other potentially toxic compounds, caution should be exercised when handling and preparing Teotaxol® solutions. The use of gloves is recommended.
If Teotaxol® or diluted solution for intravenous infusion should come into contact with the skin, immediately and thoroughly wash with soap and water. If Teotaxol® or diluted solution for intravenous infusion should come into contact with mucosa, immediately and thoroughly wash with soap and water.
Contact of the Teotaxol® 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 Teotaxol® dilution for infusion should be stored in bottles (glass, polypropylene) or plastic bags (polypropylene, polyolefin) and administered through polyethylene-lined administration sets.
- Preparation and Administration:
Teotaxol® 20 mg/ml concentrate for solution for infusion requires NO prior dilution with a solvent and is ready to add to the infusion solution.
-Each vial is of single use and should be used immediately.
-Allow the required number of boxes of Teotaxol® concentrate for solution for infusion to stand below 25°C for 5 minutes before use.
– Using only a 21-gauge needle, aseptically withdraw the required amount of Teotaxol® (20 mg docetaxel/mL) with a calibrated syringe and inject via a single injection (one shot) 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 mg/mL to 0.74 mg/ml. If a dose greater than 200 mg of Teotaxol® is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mg/ml Teotaxol® is not exceeded.
– TEOTAXOL® is compatible and Stable in D5W, LR, NS
– TEOTAXOL® is Incompatible with Amphotericin B, doxorubicin liposome, methylprednisolone sodium succinate, nalbuphine
– Thoroughly mix the infusion by gentle manual rotation and avoid foaming.
– As with all parenteral products, TEOTAXOL® should be inspected visually for particulate matter or discoloration prior to administration whenever the solution and container permit. If the TEOTAXOL® or diluted solution is not clear or appears to have precipitation, it should be discarded.
– TEOTAXOL® infusion solution is supersaturated, therefore may crystallize over time. If crystals appear, the solution must no longer be used and shall be discarded.
– The TEOTAXOL® diluted solution for infusion should be administered intravenously as a 1-hour infusion under ambient room temperature (below 30°C) and lighting conditions.
