Pediatric Oncology
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Basic Oncology

Introduction Action Definitions Drug Resistance Classification Alkylating Agents Antimetabolites Antitumor AntibioticsVinca AlkaloidsEtoposideTaxanesCamptothecinsPlatinum CompoundsOther AgentsBiotherapy Targeted Therapy Side Effects References

 

 

Brain Tumors

BM Transplant

Leukemia

Lymphoma

Sarcomas

Renal Tumors

Neuroblastoma

Late Effects

 

 

 

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These are natural products that are produced from Streptomyces bacteria.

Most are non-cell cycle specific and interfere with cellular processes

• Interfere with nucleic acid synthesis/function
• Inhibit DNA/RNA synthesis

Anthracyclines and chromomycins are two classes of antitumour antibiotics. Most are cell cycle non-specific.

 

Examples of Antitumor Antibiotics:

ANTHRACYCLINES	Daunorubicin Doxorubicin (Adriamycin) Idarubicin
ANTHRACENIDIONES	Mitoxantrone
CHROMOMYCINS	Dactinomycin
MISCELLANEOUS	Bleomycin Mitomycin

 

Anthracyclines and Anthracenidiones

Mechanism of action:

• Topoisomerase inhibitors that target topoisomerase II.
• Have intercalating activity (inserting themselves between DNA base pairs).
• Able to produce oxygen radicals and so interfere with mitochondrial function.
• These agents are cell-cycle non-specific, although they are maximally cytotoxic during S phase

Examples are doxorubicin, daunorubicin, epirubicin, idarubicin and mitoxantrone.

Daunorubicin

• Used mainly in induction treatment for leukemia, non-hodgkin lymphoma and Ewings sarcoma.
• Commonly given IV as a bolus infusion

Doxorubicin (Adriamycin)

• Broad therapeutic range including non-Hodgkin and Hodgkin lymphoma, multiple myeloma, lung, ovarian, gastric, breast, thyroid, sarcoma and paediatric malignancies.
• Given IV as a direct IV bolus infusion, an intermittent infusion over 1-6 hours  or as a continuous infusion over 24-98 hours.

 

Chromomycins

Dactinomycin

• Also known as Actinomycin-D
• Important in the treatment of pediatric solid tumours – such as Wilms and Ewings tumours and rhabdomyosarcomas, as well as gestational trophoblastic neoplasia.
• Chromophore (naturally occurring pigment) is responsible for its red-yellow colour.
• It is cell-cycle non-specific
• Works by intercalation to inhibit RNA and protein synthesis.
• Usually given as a direct IV injection.

 

Miscellaneous

Bleomycin

• cell-cycle specific (G2 and M) agent
• works by forming an iron-oxygen-bleomycin complex that then forms free radicals which cause single and double stranded DNA breaks.
• Resistance mechanisms:
• Increased bleomycin hydrolase enzyme expression
• Increased DNA repair enzymes
• Decreased drug accumulation via decreased uptake.
• Wide range of applications: Hodgkin and non-Hodgkin lymphoma, germ cell tumors, squamous cell cancers in adults.
• Given IV or IM.

Mitomycin C

• cell-cycle non-specific alkylating agent
• Potent DNA cross-linking activity.
• It is used intravenously to treat gastrointestinal and breast cancers, and intravesically in adults to treat bladder cancers.
• Due to its potential for delayed bone marrow toxicity, intravenously it is usually given in 6 week intervals. Renal failure and haemolytic uremic syndrome has been reported in a subset of patients.

 

Summary of Antiitumor Antibiotic Toxicities:

Drug	Toxicity	Special considerations
Doxorubicin Daunorubicin Idarubicin	Myelosuppression (nadir 5-10 days)   Mucositis, stomatitis   Potent cardiotoxic effects with a maximum lifetime dosage of 550 mg/m2 (350 mg/m2 if radiation to chest). Studies have shown increased risks for cardiotoxicity (cardiac failure, CHF and severe arrythmias) with cumulative doses exceeding 500mg/m2.   Radiation recall   Hepatotoxic	Echocardiograms are required periodically to monitor cardiac function Cardiac ejection fraction must be acceptable (shortening fraction >28%) Cumulative dose recording is required. Dose adjustments for renal or hepatic abnormalities and during radiation Urine may be red in colour Vesicant – severe tissue damage if extravasation occurs. Treat topically with ice +/- DMSO or systemically with dexrazoxane IV
Mitoxantrone	Cardiac arrhythmias   Radiation recall   Myelosuppression (nadir day 10)   Cardiomyopathy as for anthracyclines	Cumulative to anthracycline doses and recording required Routine echocardiograms Urine may be blue-green in colour, sclera may be blue Vesicant – severe tissue damage if extravasation occurs.  Treat topically with ice +/- DMSO or systemically with dexrazoxane IV
Actinomycin D	Nausea and vomiting   Mucositis   Myelosuppression (nadir 14-21 days)   Radiation recall, skin photosensitivitiy and hyperpigmentation	Vesicant – severe tissue damage if extravasation occurs.  Treat with ice. Dose adjustments during radiation May be ordered in micrograms, so check dose carefully
Bleomycin	Interstitial pneumonitis May present as cough, dyspnea, inspiratory crackles and infiltrates on CXR.   May result in chronic fibrosis at any time during and after therapy   Stomatitis   Hyperpigmentation of skin   Lethal anaphylactoid reactions with high fever and hypotension	Monitor pulmonary function tests at baseline and regularly throughout treatment and at follow-up Record cumulative doses (cumulative lifetime dose should not exceed 400 units) Dose adjustments if chest irradiation Test dose may be considered in lymphoma patients Scuba diving contraindicated in patients who have received bleomycin
Mitomycin C	Potential delayed myelosuppression (nadir 4-8 weeks) (usually given IV q 6 weekly).   Renal failure and haemolytic uremic syndrome has been reported in a subset of patients.	Not used in pediatrics

 

 

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