Docetaxel, Irinotecan, Recurrent, Refractory, Bone and Soft Tissue Sarcomas
Treatment setting:Hospitalization is preferred, but treatment on the outpatient base is
Regimen and premedication
1. Regimen Docetaxel 100 mg/m2 mixed in D5W or N/S IV over 60 min: Day 1 Irinotecan 80
mg/m2 mixed in D5W IV over 90 min: Days 1 and 8
2. Premedications Dexamethasone 3 mg/m2 PO or IV 12 hours and 1 hour prior to docetaxel
administration. A third dose of dexamethasone will be given 8 hours following docetaxel
infusion. Patients should not be treated with docetaxel if they did not start the PO
premedication the previous day. Parenteral pheniramine maleate may be given prior to
docetaxel if patient has had a previous hypersensitivity to the agent. If used,
pheniramine maleate (1 mg/kg IV) should be administered 30 minutes prior to infusion
and every six hours thereafter, as needed.
Treatment interval and overall treatment period : Therapy consists of 3-week cycles
comprising weekly treatment for 2 weeks (docetaxel on D1 and irinotecan on D1 and D8)
followed by 1-week rest, and will be continued in the absence of disease progression or
unacceptable toxicity. Maximal number of cycles is twelve, however, additional cycles may be
employed only when at least PR is maintained and patients want to take more.
Treatment modifications : Toxicity is evaluated according to common terminology criteria for
adverse events v3.0 (CTCAE) of the National Cancer Institute.
Next cycle is to be delayed until ANC count on the starting day of scheduled treatment is at
least 750/μL and platelet count is at least 75,000/μL, when full doses of irinotecan and
docetaxel will be given. Next cycle is also delayed if diarrhea of grade 2 or higher
(including moderate cramping) occurs on the day when the dose is due.
Irinotecan treatment of D8 will be delayed to D10 if grade 2 or higher non-hematological
toxicity occurred on the day when the dose is due. Irinotecan scheduled at D8 will be
omitted if diarrhea of grade 2 or higher occurred on the D10. Doses of docetaxel and
irinotecan in the subsequent cycles are reduced by 20% for febrile grade 4 neutropenia
(ANC<500/μL). Subsequent dose will be reduced by 20% for the recurrent toxicity. G-CSF is
allowed if clinically indicated according to the ASCO guideline (22). Dose of docetaxel in
the subsequent cycles are reduced by 20% for grade 2 neurologic toxicity/recurrent fluid
retention, or any grade 3 non-hematologic toxicities, including hepatotoxicity, peripheral
neuropathy, stomatitis, skin eruption, myalgia, cardiac events, or hypersensitivity.
Subsequent dose will be reduced by 20% for the recurrent toxicity. In patients with grade 2
or higher fluid retention syndrome, prophylactic dexamethasone will be given by 6 mg/m2 bid
for 3 days. Dose re-escalation after dose reduction is not permitted. Docetaxel and
Irinotecan (DI) treatment will be discontinued in patients with grade 4 non-hematological
toxicities at the discretion of investigators.
Dose modification schedule : Docetaxel and Irinotecan (DI) dose adjustment within a cycle
will be made following the guidelines shown in Table 1 and 2 based on weekly WBC count and
criteria for adverse events v3.0 (CTCAE).
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
CT or MRI image of tumor
2 cycles after chemotherapy (6 weeks, 1cycle = 3 weeks)
Byung-Kiu Park, M.D.,Ph.D.
Pediatric Oncology Branch, National Cancer Center, Korea
South Korea: Korea Food and Drug Administration (KFDA)