Dosing Adjustment Guidelines

The occurrence of side effects or special considerations may require Taxotere^® (docetaxel) dosing adjustments in certain individuals.¹

Dosing for metastatic breast cancer

For patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy

• Taxotere^® 60 mg/m² to 100 mg/m² IV infusion over 1 hour, administered every 3 weeks

Initial Dose	Adverse Event	Management
100 mg/m2	Febrile neutropenia, or ANC < 500 cells/mm3 > 7 days, or Severe/cumulative cutaneous reactions	Reduce Taxotere® dose to 75 mg/m2 Reduce to 55 mg/m2 if reactions persist, or discontinue Taxotere®
60 mg/m2	No febrile neutropenia, and No ANC < 500 cells/mm3 > 7 days, and No severe/cumulative cutaneous reactions	Consider increasing Taxotere® dose
60–100 mg/m2	>Grade 3 peripheral neuropathy	Discontinue Taxotere®

Dosing for early-stage breast cancer

In combination with doxorubicin and cyclophosphamide for the adjuvant treatment of patients with operable, node-positive breast cancer

• Doxorubicin 50 mg/m² and cyclophosphamide 500 mg/m² followed by Taxotere^® 75 mg/m² IV infusion over 1 hour every 3 weeks for 6 cycles (or 18 weeks)
• Taxotere^® in combination with doxorubicin and cyclophosphamide should be administered when the neutrophil count is ≥ 1500 cells/mm³
• Prophylaxis with G-CSF may be used to mitigate the potential risk of hematologic toxicities

Adverse Event	Initial Management	Management for continued Symptoms
Febrile neutropenia	Use G-CSF for subsequent cycles	Reduce Taxotere® dose to 60 mg/m2
Severe/cumulative cutaneous reactions Moderate neurosensory effects	Reduce Taxotere® dose to 60 mg/m2	Discontinue Taxotere®
Grade 3–4 stomatitis	Reduce Taxotere® dose to 60 mg/m2

Dosing for prostate cancer

In combination with prednisone for the treatment of patient with androgen-independent (hormone-refractory) metastatic prostate cancer

• Taxotere^® 75 mg/m² IV infusion over 1 hour, administered every 3 weeks
• Prednisone 5 mg orally twice daily is administered continuously
• Taxotere^® in combination with prednisone should be administered when the neutrophil count is ≥1500 cells/mm³

Adverse Event	Management
Febrile neutropenia, or ANC < 500 cells/mm3 > 7 days, or Severe/cumulative cutaneous reactions, or Moderate neurosensory effects	Reduce Taxotere® dose to 60 mg/m2. If reaction continues, discontinue Taxotere®

Dosing for non-small cell lung cancer (NSCLC)-First line

In combination with cisplatin for the treatment of patients with unresectable, locally advanced or metastatic NSCLC who have not previously received chemotherapy

• Taxotere^® 75 mg/m² IV infusion over 1 hour, immediately followed by cisplatin 75 mg/m² over 30 to 60 minutes, administered every 3 weeks

Adverse Event	Management
Platelet count nadir < 25,000 cells/mm3 in previous course, or Febrile neutropenia, or Any severe nonhematologic toxicity	Reduce Taxotere® dose to 65 mg/m2 Reduce to 50 mg/m2 if symptoms continue

Dosing for non-small cell lung cancer (NSCLC)-Second line

For patients with locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy

• Taxotere^® 75 mg/m² IV infusion over 1 hour, administered every 3 weeks

Adverse Event	Management
Febrile neutropenia, or ANC < 500 cells/mm3 > 7 days, or Severe/cumulative cutaneous reactions, or Other grade 3–4 nonhematologic toxicities	Withhold Taxotere® until toxicity resolves Resume Taxotere® at 55 mg/m2
≥ Grade 3 peripheral neuropathy	Discontinue Taxotere®

Dosing for gastric cancer

In combination with cisplatin and fluorouracil for the first-line treatment of advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction

• Taxotere^® 75 mg/m² IV infusion over 1 hour, followed by cisplatin 75mg/m² as a 1- to 3-hour IV infusion (both on day 1 only), followed by fluorouracil 750 mg/m²/day given as a 24-hour continuous IV infusion for 5 days, starting at the end of the cisplatin infusion
• Treatment is repeated every 3 weeks
• Patients must receive premedication with antiemetics and appropriate hydration for cisplatin administration

Adverse Event	Initial Management		Management for Continued Symptoms
Febrile neutropenia, or Documented infection with neutropenia, or Neutropenia > 7 days	Use G-CSF for subsequent cycles	Withhold Taxotere® until neutrophils >1500 cells/mm3 and platelets >100,000 cells/mm3	Reduce Taxotere® dose to 60 mg/m2 Reduce to 45 mg/m2 for subsequent episodes Discontinue treatment if toxicity persists
Grade 4 thrombocytopenia	Reduce Taxotere® dose to 60 mg/m2		Discontinue Taxotere®

Adverse Event	Initial Management	Management for Continued Symptoms
Grade 3 diarrhea	Reduce 5-FU dose by 20%	Reduce Taxotere® dose by 20%
Grade 4 diarrhea	Reduce Taxotere® and 5-FU doses by 20%	Discontinue all therapy
Grade 3 stomatitis/mucositis	Reduce 5-FU dose by 20%	Discontinue 5-FU Third episode: Reduce Taxotere® dose by 20%
Grade 4 stomatitis/mucositis	Discontinue 5-FU	Reduce Taxotere® dose by 20%

Dosing for head and neck cancer

In combination with cisplatin and fluorouracil for induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck

Sequential therapy with Taxotere^®, cisplatin, and fluorouracil (TPF) followed by concurrent chemoradiotherapy (CRT)

• Taxotere^® 75 mg/m² IV infusion over 1 hour on day 1, followed by cisplatin 100 mg/m² as a 30-minute to 3-hour IV infusion on day 1, followed by fluorouracil 1000 mg/m²/day given as a 24-hour continuous IV infusion on days 1–4
• Treatment is repeated every 3 weeks for 3 cycles.

Concurrent CRT

• Carboplatin (AUC 1.5) weekly; 7 doses maximum + radiation: once-daily fractionation (2 Gy/day x 1/day; 5 days/wk, 7 wks)

or

Induction therapy with Taxotere^®, cisplatin, and fluorouracil (TPF) followed by radiotherapy (RT)

• Taxotere^® 75mg/m² IV infusion over 1 hour, followed by cisplatin 75 mg/m² IV infusion over 1 hour (both on day 1 only), followed by fluorouracil 750 mg/m²/day given as a 24-hour continuous IV infusion for 5 days. Following chemotherapy, patients should receive radiotherapy
• Treatment is repeated every 3 weeks for 4 cycles
• Patients must receive premedication with atiemetics and appropriate hydration for cisplatin administration

RT

• Conventional fractionation 66-70 Gy total dose) or accelerated regimen (70 Gy total maximum dose) or hyperfractionated regimen (74 Gy total maximum dose)

Adverse Event	Initial Management		Management for Continued Symptoms
Febrile neutropenia, or Documented infection with neutropenia, or Neutropenia > 7 days	Use G-CSF for subsequent cycles	Withhold Taxotere® until neutrophils >1500 cells/mm3 and platelets >100,000 cells/mm3	Reduce Taxotere® dose to 60 mg/m2 Reduce to 45 mg/m2 for subsequent episodes Discontinue treatment if toxicity persists
Grade 4 thrombocytopenia	Reduce Taxotere® dose to 60 mg/m2		Discontinue Taxotere®

Adverse Event	Initial Management	Management for Continued Symptoms
Grade 3 diarrhea	Reduce 5-FU dose by 20%	Reduce Taxotere® dose by 20%
Grade 4 diarrhea	Reduce Taxotere® and 5-FU doses by 20%	Discontinue all therapy
Grade 3 stomatitis/mucositis	Reduce 5-FU dose by 20%	Discontinue 5-FU Third episode: Reduce Taxotere® dose by 20%
Grade 4 stomatitis/mucositis	Discontinue 5-FU	Reduce Taxotere® dose by 20%

Special Populations¹

In the hepatically impaired

Patients with bilirubin greater than the upper limit of normal (ULN) should generally not receive Taxotere^®. Also, patients with serum glutamic-oxaloacetic transaminase (SGOT) and/or serum glutamic-pyruvic transaminase (SGPT) > 1.5 x ULN concomitant with alkaline phosphatase > 2.5 x ULN should generally not receive Taxotere^®.

In pediatric patients

The safety and effectiveness of docetaxel in pediatric patients have not been established.

In geriatric patients

In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy in elderly patients.