The Expert Committee recommended the addition to the complementary list
of the EMLc of ATRA, dasatinib, fluorouracil, imatinib, irinotecan, nilotinib,
oxaliplatin, procarbazine and rituximab for the paediatric cancer indications
outlined in the table below.
The Committee also recommended the extension of the current listings
on the EMLc of bleomycin, doxorubicin, vincristine, cisplatin, cyclophosphamide,
prednisolone, cytarabine, daunorubicin, mercaptopurine, methotrexate, cytarabine
and hydroxycarbamide to include the indications outlined in the table below.
The Committee also recommended the addition to the core list of the
EMLc of enoxaparin with a square box for use as an anticoagulant in children.
The Expert Committee did not recommend the addition of zoledronic acid
to the complementary list of the EMLc for the treatment of malignancy-related
bone disease. The Committee noted that data for its use in children are scant and
fragmented. The Committee was also concerned that the effects of zoledronic acid
in some paediatric cancers (e.g. osteosarcoma) were largely negative, and that
there are insufficient long-term safety data of bisphosphonate use in paediatric
cancer patients to be reassured of an acceptable benefit–to–harm ratio.
Furthermore, the Committee noted that although use of bisphosphonates
in paediatric patients has been reported to be well tolerated, the impact of use in
the context of patients with actively growing skeleton is not yet fully known.
New medicines for EMLc
All-trans retinoic acid: Acute promyelocytic leukaemia
Dasatinib: Imatinib-resistant chronic myeloid leukaemia
Fluorouracil: Nasopharyngeal carcinoma, early-stage colon cancer, early-stage rectal cancer, metastatic colorectal cancer
Imatinib: Chronic myeloid leukaemia, gastrointestinal stromal tumour
Irinotecan: Metastatic colorectal cancer
Nilotinib: Imatinib-resistant chronic myeloid leukaemia
Oxaliplatin: Early stage colon cancer, metastatic colorectal cancer
Procarbazine: Hodgkin lymphoma
Rituximab: Diffuse large B-cell lymphoma
Enoxaparin: Anticoagulant (core list)
Extension of indications for currently listed medicines
Bleomycin: Kaposi sarcoma
Doxorubicin: Kaposi sarcoma
Vincristine: Kaposi sarcoma
Cisplatin: Nasopharyngeal carcinoma
Cyclophosphamide: Diffuse large B-cell lymphoma
Prednisolone: Diffuse large B-cell lymphoma
Cytarabine: Acute promyelocytic leukaemia, acute myelogenous leukaemia
Daunorubicin: Acute promyelocytic leukaemia
Mercaptopurine: Acute promyelocytic leukaemia
Methotrexate: Acute promyelocytic leukaemia
Hydroxycarbamide: Chronic myeloid leukaemia
The application proposed an extension of adult cancer indications to paediatrics
and corresponding inclusion on the EMLc. The proposal involves both the
inclusion of new indications for some cancer medicines currently on the EMLc
and the addition of selected new cancer and supportive care medicines to the
EMLc. (Refer to TRS 1021 for the proposed listing extensions).
The proposed medicines and corresponding indications had not previously been
considered for inclusion on the EMLc.
The application applied the following rationale in proposing the medicines
and indications for inclusion on the EMLc:
■ The medicine must already be listed on the EML or EMLc.
■ The indications listed for adults are also diagnosed in children aged
12 years and under.
■ The medicines have been reported for treatment in children aged
12 years and under for the same indication as listed on the EML for
treatment in adults.
■ Published literature supports the extension of the indication to
children, including clinical studies, peer-reviewed consensus
documents and/or clinical guidelines support the medicine’s role as
standard of care.
Public health relevance
Cancer is a leading cause of death for children globally with the most common
cancer types occurring in children being leukaemias, lymphomas and central
nervous system tumours (1). Childhood cancers generally cannot be prevented
nor screened for, so improving outcomes for children with cancer relies on early
and accurate diagnosis and access to effective treatments.
In 2018, WHO launched the Global Initiative for Childhood Cancer,
to provide leadership and technical assistance to Member States to build and
sustain high quality childhood cancer programmes. The goal of this initiative is
to achieve at least 60% survival for all children with cancer globally by 2030 (2).
Acute promyelocytic leukaemia (APML)
New medicine: all-trans retinoic acid (ATRA)
New indication: cytarabine, daunorubicin, mercaptopurine, methotrexate
The median age of children with APML has been reported as 10 years (3).
Standard regimens used for children with APML include ATRA (3, 4), with
prior randomized trial data demonstrating significant disease-free survival
improvement for children randomized to receive ATRA vs not (48% at 5 years,
vs 0%, p<0.0001), with overall survival rates sustained at 10 years (5). The use
of ATRA is acknowledged in standard guidelines for the treatment of APML,
and is considered to be a paradigm for a targeted approach to the treatment of
leukaemia (6–10). The treatment of APML is typically provided in the context
of poly-chemotherapy, involving cytarabine, daunorubicin, mercaptopurine and
Acute myeloid leukaemia (AML)
New indication: cytarabine
The safety and effectiveness of cytarabine for the treatment of childhood AML
have been evaluated in controlled clinical trials (11–13). It is considered the
standard of care, used internationally for children with AML, as in adults (14, 15).
Chronic myeloid leukaemia (CML)
New medicines: imatinib, dasatinib, nilotinib, hydroxycarbamide
CML is a very rare disease in children, estimated to be responsible for 2% of all
leukaemias in children less than 15 years of age with an annual incidence of one
case per million children in that age range (16). The tyrosine kinase inhibitors
introduced a chance of cure for CML, with long lasting disease control and
significantly improved outcomes (17).
Imatinib has shown clinical benefit in children with CML, with results
comparable to those seen in adults (18). In particular, a clinical study of the
use of imatinib in patients aged less than 18 years with CML in the chronic
phase demonstrated the efficacy, safety and long-term benefit of imatinib in
Dasatinib and nilotinib have been used in children with CML including
(but not limited to) imatinib-resistant cases. A Phase II trial of dasatinib in 113
paediatric patients with CML demonstrated a complete cytogenetic response was
achieved in 76% of imatinib-resistant patients, with an acceptable safety profile
that did not include pleural or pericardial effusion, commonly seen in dasatinibtreated adults (20). The effectiveness and safety of nilotinib in children with CML
has also been reported (21). Nilotinib has been approved by the United States
FDA for treatment of paediatric patients with newly diagnosed or resistant CML
on the basis of the results from two open-label, single-arm trials involving 69
patients (22, 23). For imatinib-resistant patients, the major molecular response
rate was 40.9%. No new safety concerns were reported, noting transient and
manageable laboratory abnormalities: hyperbilirubinaemia and moderate to
Hydroxycarbamide has a recognized debulking/cytoreductive role for
myeloid malignancies and for palliative purpose in all settings. In addition,
hydroxycarbamide can have an important role in settings where resource
limitations affect access to imatinib or other tyrosine kinase inhibitors, to allow
commencement of antineoplastic therapy (24). A general expert consensus
recommendation for childhood CML includes hydroxycarbamide as standard
initial therapy in all settings, while awaiting confirmatory diagnostic testing
results as well as initial clinical response (25).
Gastrointestinal stromal tumour (GIST)
New medicine: imatinib
Imatinib is the preferred treatment for molecularly-selected GIST in adults and
children, where c-KIT sensitive mutations are demonstrated. Paediatric GISTs
represent a distinct entity, and may be associated with genetic syndromes (such
as Carney Triad, Carney-Stratakis syndrome or neurofibromatosis 1 (NF1)/
Von Recklinghausen disease). It is also less common for paediatric patients
with GIST to have the activating mutations in KIT and platelet-derived growth
factor receptor alpha (PDGFRA) seen in adults. Data on the effectiveness and
activity of imatinib in paediatric GIST is scarce, as it is a very rare entity (1–2%
of all the cases). Children less than 18 years of age typically have more indolent
disease with more favourable prognosis than in adults (approximating 100%
five-year overall survival), as reported in a long-term retrospective analysis of
a large observational study, that included a sub-group of 28 patients in this age
Diffuse large B-cell lymphoma (DLBCL)
New medicine: rituximab
New indication: cyclophosphamide, doxorubicin, prednisolone, vincristine
Different studies of DLBCL have established a role for rituximab in paediatric
populations, with studies often spanning all age groups including adults and
children starting at age 9 years (27), and confirming efficacy and safety in children
(28). Rituximab is administrated in the context of a combination regimen with
CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) (27, 28).
CHOP alone may be administered in settings where rituximab is not available.
New indication: bleomycin, doxorubicin, vincristine
Kaposi sarcoma in children primarily occurs as either endemic (HIV-unrelated)
or epidemic (HIV-related) disease. According to the data known from registries
and literature, Kaposi’s sarcoma primarily occurs in the elderly population of the
Mediterranean region, while the occurrence in children is restricted to smaller
series (29). Data from paediatric cohorts and clinical trials showed a median age
of diagnosis at 8 years old. Chemotherapy indicated for Kaposi sarcoma includes
bleomycin, vincristine and doxorubicin (30–34). One of the regimens combining
doxorubicin, bleomycin and vincristine (ABV) has reported 80% remission for
stage I HIV-positive patients treated in South Africa (32). Bleomycin, vincristine
and doxorubicin have also been included as standard treatment agents in
international expert consensus recommendations (35).
New indication: cisplatin, fluorouracil
Nasopharyngeal carcinoma (NPC) is the most commonly diagnosed head
and neck malignant neoplasm in China and South-East Asian countries, but
is considered relatively rare among children. Treatment schemes are typically
adapted for children from adult-based regimens. Cisplatin-based regimens are
the standard of care for children with NPC. Together with cisplatin, fluorouracil
(5-FU) is included in standard regimens for children with NPC, with standard
administration of two courses 21 days apart (36–39). The use of cisplatin
including as a radiosensitizer (with concomitant cisplatin and radiation therapy)
following cisplatin/5-FU in the systemic treatment of NPC in children is
recognized as standard across different institutions and countries, extrapolating
from the adult treatment experience (40–43).
Colon and rectal cancers
New medicine: irinotecan, oxaliplatin
New indication: cisplatin, fluorouracil
While very rare, colorectal cancers can occur in children (reported in as young
as nine months old) and typically utilize the same chemotherapy agents as in
adults, including 5-FU for the neoadjuvant treatment of rectal cancer, 5-FU and
oxaliplatin for the adjuvant treatment of colon and rectal tumours, and 5-FU,
oxaliplatin and irinotecan for advanced or metastatic colorectal cancer (44–47).
New medicine: procarbazine
Procarbazine is commonly included as a drug of choice in children for the
treatment of Hodgkin lymphoma. According to clinical guidelines and literature,
procarbazine is a standard inclusion in multi-agent chemotherapy regimens
for Hodgkin lymphoma in children (48, 49). For the paediatric population,
multiple regimens containing procarbazine are used, in particular BEACOPP
that contains bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine,
procarbazine, and prednisone. It is often used in more resource-limited settings.
Local selection and use should consider known gonadotoxicity and effects on
male fertility (50).
Malignancy-related bone disease
New medicine: zoledronic acid
Although certain malignancy-related bone diseases, such as osteonecrosis, occur
more often in older children, patients as young as age 4 to 6 years have been
affected and required treatment (51–53). The administration of zoledronic acid
in paediatric oncology appears safe, and may result in improved bone strength
and pain control. In a retrospective chart review of inpatients and outpatients
less than 21 years old who received zoledronic acid at the Children's Hospital of
Philadelphia, safety of the bisphosphonate was assessed. The safety profile was
consistent with the known experience in adults, including preventable alterations
in calcium levels, with no major side-effects reported (51).
New medicines: enoxaparin
The use of low molecular weight heparin (LMWH) as an anticoagulant is
considered standard of care for prophylaxis and treatment in children, including
but not limited to children with cancer. Malignancy as well as treatment-related
factors such as immobilization and central venous access can increase risk for
thrombosis (54). Enoxaparin as standard antithrombotic therapy is used as a first
option in routine practice in many settings (55–57).
Not reported separately in the application.
A randomized, multicentre, open-label Phase III trial (OS2006) compared
standard chemotherapy with or without zoledronic acid in 318 patients aged
between 5 years and 50 years (median 15.5 years) with newly diagnosed highgrade osteosarcoma (58). The trial results indicated that zoledronic acid did not
improve event-free survival, percentage of good histological response or overall
survival. No significant differences in toxicity or orthopaedic complications
were observed between treatment groups. The trial was stopped after the second
interim analysis for futility and the authors concluded that the use of zoledronic
acid in osteosarcoma patients was not recommended.
A retrospective analysis of the use of zoledronic acid for treatment
of chemotherapy related osteonecrosis in 20 children and adolescents with
osteonecrosis found that zoledronic acid was well tolerated and improved joint
pain in the majority of patients (53). However, among patients with osteonecrosis
of the hip, the majority had progressive joint destruction requiring arthroplasty,
despite treatment with zoledronic acid.
Cost / cost effectiveness
Not reported in the application.
The proposed medicines are already included on the EML and/or EMLc.
The Expert Committee recognized the public health need for access to cancer
therapies for children. The Committee acknowledged that there is limited clinical
trial evidence available for the use of many cancer medicines in children, and
that it is often necessary to rely on extrapolated data from trials in adults, clinical
consensus and/or clinical practice guidelines, that lend support to a medicine’s
role as the standard of care in paediatric patients.
Comments on the application were received from the WHO Department of
Management of NCDs, Disability, Violence & Injury Prevention. The technical
unit advised that it supports the proposal to extend the listing of specified cancer
medicines and indications on the EML to the EMLc.
1. Steliarova-Foucher E, Colombet M, Ries LAG, Moreno F, Dolya A, Bray F et al. International
incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol.
2. Cancer in children. Fact Sheet [website]. Geneva: World Health Organization; 2018. (https://www.
who.int/news-room/fact-sheets/detail/cancer-in-children, accessed 29 September 2019).
3. Testi AM, Pession A, Diverio D, Grimwade D, Gibson B, de Azevedo AC et al. Risk-adapted treatment
of acute promyelocytic leukemia: results from the International Consortium for Childhood APL.
4. Zhang L, Zou Y, Chen Y, Guo Y, Yang W, Chen X et al. Role of cytarabine in paediatric acute
promyelocytic leukemia treated with the combination of all-trans retinoic acid and arsenic
trioxide: a randomized controlled trial. BMC Cancer. 2018;18(1):374.
5. Gregory J, Kim H, Alonzo T, Gerbing R, Woods W, Weinstein H et al. Treatment of children with
acute promyelocytic leukemia: results of the first North American Intergroup trial INT0129. Pediatr
Blood Cancer. 2009;53(6):1005–10.
6. Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E et al. A randomized comparison
of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the
role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European
APL Group. Blood. 1999;94(4):1192–200.
7. Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A et al. All-trans-retinoic
acid in acute promyelocytic leukemia. N Engl J Med. 1997;337(15):1021–8.
8. Imaizumi M, Tawa A, Hanada R, Tsuchida M, Tabuchi K, Kigasawa H et al. Prospective study of a
therapeutic regimen with all-trans retinoic acid and anthracyclines in combination of cytarabine
in children with acute promyelocytic leukaemia: the Japanese childhood acute myeloid leukaemia
cooperative study. Br J Haematol. 2011;152(1):89–98.
9. Sanz MA, Grimwade D, Tallman MS, Lowenberg B, Fenaux P, Estey EH et al. Management of acute
promyelocytic leukemia: recommendations from an expert panel on behalf of the European
LeukemiaNet. Blood. 2009;113(9):1875–91.
10. Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, et al. Retinoic acid and arsenic
trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111-21.
11. Creutzig U, Ritter J, Zimmermann M, Reinhardt D, Hermann J, Berthold F et al. Improved treatment
results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose
cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Munster
93. J Clin Oncol. 2001;19(10):2705–13.
12. Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D et al. A randomized study of highdose cytarabine in induction in acute myeloid leukemia. Blood. 1996;87(5):1710–7.
13. Wells RJ, Woods WG, Lampkin BC, Nesbit ME, Lee JW, Buckley JD et al. Impact of high-dose
cytarabine and asparaginase intensification on childhood acute myeloid leukemia: a report
from the Childrens Cancer Group. J Clin Oncol. 1993;11(3):538–45.
14. De Moerloose B, Reedijk A, de Bock GH, Lammens T, de Haas V, Denys B et al. Responseguided chemotherapy for pediatric acute myeloid leukemia without hematopoietic stem cell
transplantation in first complete remission: Results from protocol DB AML-01. Pediatr Blood
15. Rasche M, Zimmermann M, Borschel L, Bourquin JP, Dworzak M, Klingebiel T et al. Successes and
challenges in the treatment of pediatric acute myeloid leukemia: a retrospective analysis of the
AML-BFM trials from 1987 to 2012. Leukemia. 2018;32(10):2167–77.
16. Ries LAG, Smith MA, Gurney JG, Linet M, Tamra T, Young JL et al. Cancer Incidence and Survival
among Children and Adolescents: United States SEER Program 1975-1995 (NIH Pub. No. 99-4649).
Bethesda: National Cancer Institute; 1999.
17. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM et al. Efficacy and safety of a
specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med.
18. Suttorp M, Schulze P, Glauche I, Gohring G, von Neuhoff N, Metzler M et al. Front-line imatinib
treatment in children and adolescents with chronic myeloid leukemia: results from a phase III
trial. Leukemia. 2018;32(7):1657–69.
19. Giona F, Santopietro M, Menna G, Putti MC, Micalizzi C, Santoro N et al. Real-Life Management of
Children and Adolescents with Chronic Myeloid Leukemia: The Italian Experience. Acta Haematol.
20. Gore L, Kearns PR, de Martino ML, Lee, De Souza CA, Bertrand Y et al. Dasatinib in Pediatric Patients
With Chronic Myeloid Leukemia in Chronic Phase: Results From a Phase II Trial. J Clin Oncol.
21. Kurosawa H, Tanizawa A, Muramatsu H, Tono C, Watanabe A, Shima H et al. Sequential use of
second-generation tyrosine kinase inhibitors following imatinib therapy in pediatric chronic
myeloid leukemia: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group.
Pediatr Blood Cancer. 2018;65(12):e27368.
22. A Pharmacokinetic (PK) Study of Nilotinib in Pediatric Patients With Philadelphia Chromosomepositive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphoblastic Leukemia (ALL)
(ClinicalTrials.gov Identifier NCT01077544). Bethesda: U.S. National Library of Medicines; 2016.
Available from https://clinicaltrials.gov/ct2/show/study/NCT01077544, accessed 29 September
23. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia
Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients (Dialog) (ClinicalTrials.
gov Identifier: NCT01844765). Bethesda: U.S. National Library of Medicine; 2018. Available from
https://clinicaltrials.gov/ct2/show/NCT01844765, accessed 29 September 2019.
24. Kiarie GW, Othieno-Abinya NA, Riyat MS. The GLIVEC international patient assistance programme:
the Nairobi experience. East Afr Med J. 2009;86(12 Suppl):S106–7.
25. Andolina JR, Neudorf SM, Corey SJ. How I treat childhood CML. Blood. 2012;119(8):1821–30.
26. Call J, Walentas CD, Eickhoff JC, Scherzer N. Survival of gastrointestinal stromal tumor patients in
the imatinib era: life raft group observational registry. BMC Cancer. 2012;12:90.
27. Giulino-Roth L, O'Donohue T, Chen Z, Bartlett NL, LaCasce A, Martin-Doyle W et al. Outcomes
of adults and children with primary mediastinal B-cell lymphoma treated with dose-adjusted
EPOCH-R. Br J Haematol. 2017;179(5):739–47.
28. Egan G, Goldman S, Alexander S. Mature B-NHL in children, adolescents and young adults: current
therapeutic approach and emerging treatment strategies. Br J Haematol. 2019;185(6):1071–85.
29. El-Mallawany NK, McAtee CL, Campbell LR, Kazembe PN. Pediatric Kaposi sarcoma in context
of the HIV epidemic in sub-Saharan Africa: current perspectives. Pediatric Health Med Ther.
30. Chagaluka G, Stanley C, Banda K, Depani S, Nijram’madzi J, Katangwe T et al. Kaposi’s sarcoma in
children: an open randomised trial of vincristine, oral etoposide and a combination of vincristine
and bleomycin. Eur J Cancer. 2014;50(8):1472–81.
31. Macken M, Dale H, Moyo D, Chakmata E, Depani S, Israels T et al. Triple therapy of vincristine,
bleomycin and etoposide for children with Kaposi sarcoma: Results of a study in Malawian
children. Pediatr Blood Cancer. 2018;65(2).
32. Hesseling PB, Katayi E, Wharin P, Bardin R, Kouya F, Palmer D et al. Kaposi’s sarcoma: Good
outcome with doxorubicin, bleomycin and vincristine sulphate (ABV) chemotherapy and highly
active antiretroviral therapy. S Afr Med J. 2017;107(11):952–3.
33. Cox CM, El-Mallawany NK, Kabue M, Kovarik C, Schutze GE, Kazembe PN et al. Clinical characteristics
and outcomes of HIV-infected children diagnosed with Kaposi sarcoma in Malawi and Botswana.
Pediatr Blood Cancer. 2013;60(8):1274–80.
34. Stefan DC, Stones DK, Wainwright L, Newton R. Kaposi sarcoma in South African children. Pediatr
Blood Cancer. 2011;56(3):392–6.
35. Molyneux E, Davidson A, Orem J, Hesseling P, Balagadde-Kambugu J, Githanga J et al. The
management of children with Kaposi sarcoma in resource limited settings. Pediatr Blood Cancer.
36. Casanova M, Bisogno G, Gandola L, Cecchetto G, Di Cataldo A, Basso E et al. A prospective protocol
for nasopharyngeal carcinoma in children and adolescents: the Italian Rare Tumors in Pediatric
Age (TREP) project. Cancer. 2012;118(10):2718–25.
37. Casanova M, Ozyar E, Patte C, Orbach D, Ferrari A, Veyrat-Follet C et al. International randomized
phase 2 study on the addition of docetaxel to the combination of cisplatin and 5-fluorouracil
in the induction treatment for nasopharyngeal carcinoma in children and adolescents. Cancer
Chemother Pharmacol. 2016;77(2):289–98.
38. Buehrlen M, Zwaan CM, Granzen B, Lassay L, Deutz P, Vorwerk P et al. Multimodal treatment,
including interferon beta, of nasopharyngeal carcinoma in children and young adults:
preliminary results from the prospective, multicenter study NPC-2003-GPOH/DCOG. Cancer.
39. Mertens R, Granzen B, Lassay L, Bucsky P, Hundgen M, Stetter G et al. Treatment of nasopharyngeal
carcinoma in children and adolescents: definitive results of a multicenter study (NPC-91-GPOH).
40. Radhakrishnan V, Kumar P, Totadri S, Ganesan P, Selvaluxmy G, Ganesan T et al. Pediatric
nasopharyngeal carcinoma: Experience from a tertiary cancer center in India. Indian J Cancer.
41. Khalil EM, Anwar MM. Treatment results of pediatric nasopharyngeal carcinoma, NCI, Cairo
University experience. J Egypt Natl Canc Inst. 2015;27(3):119–28.
42. Liu W, Tang Y, Gao L, Huang X, Luo J, Zhang S et al. Nasopharyngeal carcinoma in children and
adolescents - a single institution experience of 158 patients. Radiat Oncol. 2014;9:274.
43. Gonzalez-Motta A, Gonzalez G, Bermudez Y, Maldonado MC, Castaneda JM, Lopez D et al. Pediatric
Nasopharyngeal Cancer: Case Report and Review of the Literature. Cureus. 2016;8(2):e497.
44. Saab R, Furman WL. Epidemiology and management options for colorectal cancer in children.
Paediatr Drugs. 2008;10(3):177–92.
45. Hill DA, Furman WL, Billups CA, Riedley SE, Cain AM, Rao BN et al. Colorectal carcinoma in
childhood and adolescence: a clinicopathologic review. J Clin Oncol. 2007;25(36):5808–14.
46. Kim ST, Choi YJ, Park KH, Oh SC, Seo JH, Shin SW et al. Capecitabine monotherapy as salvage
treatment after failure of chemotherapy containing oxaliplatin and irinotecan in patients with
metastatic colorectal cancer. Asia Pac J Clin Oncol. 2011;7(1):82–7.
47. Goldberg J, Furman WL. Management of colorectal carcinoma in children and young adults.
J Pediatr Hematol Oncol. 2012;34 Suppl 2:S76–9.
48. Geel JA, Chirwa TC, Rowe B, Eyal KC, Omar F, Stones DK et al. Treatment outcomes of children
with Hodgkin lymphoma between 2000 and 2010: First report by the South African Children’s
Cancer Study Group. Pediatr Blood Cancer. 2017;64(10).
49. Radhakrishnan V, Dhanushkodi M, Ganesan TS, Ganesan P, Sundersingh S, Selvaluxmy G et al.
Pediatric Hodgkin Lymphoma Treated at Cancer Institute, Chennai, India: Long-Term Outcome.
J Glob Oncol. 2017;3(5):545–54.
50. Dorffel W, Riepenhausen M, Luders H, Bramswig J. Late Effects Following Treatment of Hodgkin
Lymphoma During Childhood and Adolescence. Results of the Hodgkin Lymphoma Late Effects
Research Project. Klin Padiatr. 2016;228(6-07):286–93.
51. Bowden SA, Mahan JD. Zoledronic acid in pediatric metabolic bone disorders. Transl Pediatr.
52. Padhye B, Dalla-Pozza L, Little D, Munns C. Incidence and outcome of osteonecrosis in children
and adolescents after intensive therapy for acute lymphoblastic leukemia (ALL). Cancer Med.
53. Padhye B, Dalla-Pozza L, Little DG, Munns CF. Use of zoledronic acid for treatment of chemotherapy
related osteonecrosis in children and adolescents: a retrospective analysis. Pediatr Blood Cancer.
54. Monagle P, Chan AKC, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Gottl U et al.
Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice
Guidelines. Chest. 2012;141(2 Suppl):e737S–e801S.
55. Malhotra P, Jain S, Kapoor G. Symptomatic Cerebral Sinovenous Thrombosis Associated With
L-Asparaginase In Children With Acute Lymphoblastic Leukemia: A Single Institution Experience
Over 17 Years. J Pediatr Hematol Oncol. 2018;40(7):e450–e3.
56. Fan JL, Roberts LE, Scheurer ME, Yee DL, Shah MD, Lee-Kim YJ. Association of outcomes and anti-Xa
levels in the treatment of pediatric venous thromboembolism. Pediatr Blood Cancer. 2017;64(11).
57. Goldenberg NA, Takemoto CM, Yee DL, Kittelson JM, Massicotte MP. Improving evidence
on anticoagulant therapies for venous thromboembolism in children: key challenges and
opportunities. Blood. 2015;126(24):2541–7.
58. Piperno-Neumann S, Le Deley MC, Redini F, Pacquement H, Marec-Berard P, Petit P et al.
Zoledronate in combination with chemotherapy and surgery to treat osteosarcoma (OS2006): a
randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2016;17(8):1070–80.