Irinotecan

Generic name
Irinotecan
Brand name
ATC Code
L01CE02
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Irinotecan

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

The following kinetic parameters have been found in children and adults aged from 18 months to 27 years after administration of 20 mg/m² [DuBois 2012; Furman 2012; McGregor 2012]
Cl: 3.8-42.7 l/hour/m²
Vd: 105.4-143 l/m²

After administration of 50 mg/m² in children and adults aged 1-23 years, the following parameters were found [Bomgaars 2007]:
Cmax: 726 ± 482 ng/ml
t½: 4.7 ± 2.3 hours

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Recurrent or refractory solid tumours, including neuroblastoma, hepatoblastoma, Ewing sarcoma, rhabdomyosarcoma and Wilms' tumour
  • Intravenous
    • 1 month up to 18 years

      • The dosage and dosing frequency of oncological agents depend on the condition and are very much subject to new insights. Oncological drugs are often used in combinations. For this reason, please refer to the details treatment protocols (see www.skion.nl)

        The following indicative dosage has been stated in the literature:
        - 50 mg/m²/dose on days 1-5, max 100 mg/dose. Repeat every 3 weeks.

        • Neuroblastoma: combine irinotecan with other oncolytics. There are several options for this in the literature [7-9].
        • Hepatoblastoma: combine irinotecan with vincristine [10,11,21].
        • Ewing sarcoma: good results have been achieved combining irinotecan with temozolomide [12-15].
        • Rhabdomyosarcoma: good results have been achieved combining irinotecan with vincristine [12-15].
        • Wilms’ tumour: good results have been achieved combining irinotecan with vincristine, temozolomide and bevacizumab [20].

        Treatment by a paediatric specialist (oncologist) who has experience with using irinotecan for these indications.

Renal impaiment in children > 3 months

The dose does not need to be adjusted for renal function disorders

Patients on dialysis

No generalized recommendations are given.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects

No information is present at this moment.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Polymorphism UGT1A1A1*28 has been demonstrated to have no influence on the toxicity of irinotecan in children [Wagner 2015].

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Vinca alkaloids and analogues
L01CA01
L01CA02
Podophyllotoxin derivatives
L01CB01
L01CB02
Taxanes
L01CD02

References

  1. DuBois SG et al. , Phase I study of vincristine, irinotecan, and ¹³¹I-metaiodobenzylguanidine for patients with relapsed or refractory neuroblastoma: a new approaches to neuroblastoma therapy trial. , Clin Cancer Res. , 2012, May 1;18(9), 2679-86
  2. Furman WL et al., A single-arm pilot phase II study of gefitinib and irinotecan in children with newly diagnosed high-risk neuroblastoma., Invest New Drugs., 2012, Aug;30(4), 1660-70
  3. McGregor LM et al., Dose escalation of intravenous irinotecan using oral cefpodoxime: a phase I study in pediatric patients with refractory solid tumors., Pediatr Blood Cancer., 2012, Mar;58(3), 372-9
  4. Bomgaars LR et al., Phase II trial of irinotecan in children with refractory solid tumors: a Children's Oncology Group Study., J Clin Oncol., 2007, Oct 10;25(29), 4622-7
  5. DuBois SG et al., Phase I/II study of (131)I-MIBG with vincristine and 5 days of irinotecan for advanced neuroblastoma., Br J Cancer., 2015, Feb 17;112(4), 644-9
  6. Kushner BH et al., High-dose cyclophosphamide-irinotecan-vincristine for primary refractory neuroblastoma., Eur J Cancer., 2011, Jan;47(1), 84-9
  7. Kushner BH et al., High-dose carboplatin-irinotecan-temozolomide: treatment option for neuroblastoma resistant to topotecan., Pediatr Blood Cancer., 2011, Mar;56(3), 403-8
  8. SKION. , Behandeladvies recidief hepatoblastoom. , www.skion.nl, Maart 2011
  9. Zhang YT et al., Vincristine and irinotecan in children with relapsed hepatoblastoma: a single-institution experience., Pediatr Hematol Oncol., 2015, Feb;32(1), 18-25
  10. Casey DA et al., Irinotecan and temozolomide for Ewing sarcoma: the Memorial Sloan-Kettering experience., Pediatr Blood Cancer., 2009, Dec;53(6), 1029-34
  11. Kurucu N et al., Irinotecan and temozolamide treatment for relapsed Ewing sarcoma: a single-center experience and review of the literature., Pediatr Hematol Oncol., 2015, Feb;32(1), 50-9
  12. Wagner LM et al., Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma., Pediatr Blood Cancer., 2007, Feb;48(2), 132-9
  13. Wagner LM et al., Fifteen years of irinotecan therapy for pediatric sarcoma: where to next?, Clin Sarcoma Res., 2015, Aug 28;5, 20
  14. Centre Oscar Lambret., Clinical study protocol: International randomized phase II trial of the combination of vincristine and irinotecan with or without temozolomide (VI of VIT) in children and adults with refractory of relapsed rhabdomyosarcoma., ClinicalTrials.gov identifier: NCT01355445. www.skion.nl
  15. Hawkins DS et al., Vincristine, dactinomycin, cyclophosphamide (VAC) versus VAC/V plus irinotecan (VI) for intermediate-risk rhabdomyosarcoma (IRRMS): A report from the Children’s Oncology Group Soft Tissue Sarcoma Committee., J Clin Oncol, 2014, 32:5s, (suppl; abstr 10004)
  16. Mascarenhas L et al., Randomized phase II window trial of two schedules of irinotecan with vincristine in patients with first relapse or progression of rhabdomyosarcoma: a report from the Children's Oncology Group., J Clin Oncol., 2010, Oct 20;28(30), 4658-63
  17. Pappo AS et al., Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children's Oncology Group., J Clin Oncol., 2007, Feb 1;25(4), 362-9
  18. Venkatramani R et al., Treatment of multiply relapsed wilms tumor with vincristine, irinotecan, temozolomide and bevacizumab., Pediatr Blood Cancer., 2014, Apr;61(4), 756-9
  19. Katzenstein HM et al., Upfront window vincristine/irinotecan treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 study committee, Cancer, 2017, Jun 15;123(12), 2360-2367
  20. Hol JA et al., Irinotecan for relapsed Wilms tumor in pediatric patients: SIOP experience and review of the literature-A report from the SIOP Renal Tumor Study Group, Pediatr Blood Cancer, 2018, Feb;65(2)
  21. DuBois SG et al., Phase I study of vincristine, irinotecan, and ¹³¹I-metaiodobenzylguanidine for patients with relapsed or refractory neuroblastoma: a new approaches to neuroblastoma therapy trial., Clin Cancer Res., 2012, May 1;18(9), 2679-86
  22. SKION., Behandeladvies recidief hepatoblastoom., www.skion.nl, Maart 2011

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