Chemotherapy

FST is an educational resource, if you would like further information on chemotherapies used in cancer treatment, please visit the British National Formulary (BNF)https://bnf.nice.org.uk/

Supporting Images of Chemotherapy

The main modes of actions for chemotherapy

The phases involved in chemotherapy: induction, consolidation and maintenance

One of the main ways in which chemotherapy is administered is via IV infusion, where chemotherapy is added as a drip, or via a PICC line or port-a-cath.

An example of a chemotherapy schedule where there is two weeks of chemotherapy and then one week rest. However, the amount of time for the chemotherapy to be administered depends on the drug.

A schedule for patients with lymphoma, for example, and length of time and dose information is provided per chemotherapeutic regimen(Nair et al., 2007)

The structure of the brainstem. The brain stem is the elongated part that connects with the spinal cord. It is divided into the midbrain, pons and medulla oblongata. The pons and medulla oblongata is known as the bulbar area. The midbrain is where it connects the cerebral hemispheres (right and left that contains the lobes which have major functions in the human body from thought, judgement, memory, language and understanding. The chemoreceptor trigger zone otherwise known as the prostema is where there are regulator centres for vomiting etc.

The five major classes of hepatitis viruses that are screened prior to chemotherapy. They vary in structure and influences their respective transmission route, incubation period, function thought they are all associated with the inflammation of the liver and affecting the immune function.

An introduction to the role of the MUGA scan

The percentage references ranges for the amount of blood pumped out of the heart. This is measured via the MUGA scan.

Heart failure is when the pumping action of the heart is malfunctioned because there is damage to the ventricular muscular wall which is the muscle that surrounds the bottom chambers of the heart. An alternative reason is the little doors called valves that prevent backflow and open when there is an increase in pressure or the chamber is filled with blood that pushes the blood to enter. This image presents left ventricular failure where there is accumulation of fluid and congestion due to decrease arterial blood from the heart. The effect of heart failure on the ejection fraction is illustrated. If there is lower ejection fraction, the size of the lower left chamber (left ventricle) has thin wall, weak muscle, large sized chamber reducing the ability of the heart to pump. On the other hand, if the ejection fraction is preserved in heart failure, then the size of the ventricle becomes normal or decrease in size. The walls maintain their thickness just like normal left ventricle and has a normal pumping capacity. However, the heart muscle is stiff and more pressure is needed to fill the ventricle.

The cardiac cycle presents the main steps involved in how the heart pumps blood. The top chambers are called atria and the bottom chambers are called ventricles. systole is activation whereas diastole is rest. The cycle begins with the contraction or activation of the atria that forces blood to enter the ventricles via little doors called valves (atrioventricular). The ventricles then contract or activate and push the blood out of the heart via little doors called valves (semilunar – bicuspid and tricuspid).

The echocardiogram is a type of scan that also measures how the heart beats using ultrasound waves to help detect heart conditions. However, there is no contrasting agent is used that commonly occurs in MUGA scan

An audiogram chart where it measures the loudness, degree of hearing loss and pitch of sound.

An audiometer with head phones to test hearing

Main Types Of Chemotherapy

Common chemotherapies used in bone cancer Download

Supporting Images Of Chemotherapy

The structure of a nucleotide that makes up the DNA

The process of cells dividing and replicating

Topoisomerase is an enzyme that is pivotal in DNA synthesis. Topoisomerases unwind the DNA and make a cleavage site to facilitate DNA transcription and replication. Topoisomerases can tighten the DNA (positive coiling) or separate the strands (negative coiling). Topoisomerase 1 makes one cleavage site on the DNA strand. Topoisomerase 2 makes cleavage sites on both DNA strands. Key examples of topoisomerase inhibitors are camptothecin for a topoisomerase 1 inhibitor (a) and etoposide for a topoisomerase 2 inhibitor (b). The topoisomerase inhibitors are presented as a green rectangle. They bind to nucleotide bases on either side of the cleavage site. The hydrogen bonds are presented with orange circles and dashed green lines.

Antimetabolites like methotrexate inhibit the enzyme DHFR (dihydrofolate reductase), which is fundamental in Vitamin B9 (folate) metabolism. This is vital for the production of nucleotide bases that make RNA and DNA bases.

Alternative presentation of how the antimetabolites work

About Mifamurtide

It is a type of targeted therapy that is prescribed for patients between 2 and 30 years old.
It is commonly given with chemotherapy after surgery.

The aim is to remove residual micrometastases that were not taken by chemotherapy after surgery (adjuvant chemotherapy).

The purpose of Adjuvant Therapy is to decrease the rate of local recurrence after having a curettage. This prevents the need for additional resectional and reconstruction surgeries.

How does it work?
It aims to boost the immune system, specifically macrophages and monocytes.
It is involved in the signalling pathways that are involved in cellular growth, proliferation, and other cellular functions.
The activation of NFKB and MAPK promotes inflammation and the release of small proteins called cytokines.

What examples of receptors are involved in how Mifamurtide works?

There are pattern-recognition molecules that are detectable by Toll-like receptors and oligomerization domain (NOD)-like receptors (NOD1, NOD2 and NLRP3).

They are sensitive and can recognise particular aspects in the peptidoglycan polymer found in the wall of the bacteria.

The NOD2 receptor and MDP

NOD2 is tissue-specific and can be found in monocytes, macrophages, dendritic cells, and in the wall of the cells of the intestines called Paneth cells.

A key example of a pattern-recognition molecule is muramyl dipeptide (MDP) found in the wall. This links to the source of Mifamurtide (L-MTP-PE) is a synthetic drug and a derivative of muramyl dipeptide (MDP) found in the wall of bacteria.

There are two types of intestines: large and small.

The Paneth cells are found throughout the small intestine (duodenum, jejunum and ileum) in small pouches called crypts of Lieberkühn.

The function of the small intestine is to break down and absorb food into the blood to target cells.

Paneth cells help make small proteins called defensins which has a antimicrobial effect on bacteria and other microorganisms that cause disease (pathogenic) and do not cause disease (non-pathogenic, commensal flora).

Proinflammatory cytokines released are interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor (TNF-α), chemokines, antimicrobial peptides, and adhesion molecules.

NOD-like receptors also recognise that NFKB signalling can have an amino-terminal caspase recruitment domain.

Consequently, it increases the levels of C-reactive protein and neopterine in the blood, indicating inflammation.

When is Mifamurtide given?
It is given intravenously via a vein in the blood, with breaks between cycles, at a dose of 2 mg/m2.
Each cycle lasts a week, and this treatment is given for 9 months (36 cycles) using the method stated below for the first 12 weeks.

After 12 weeks, it transfers to once a week for the next 24 weeks.

Please click here for more info via Cancer Research UK https://www.cancerresearchuk.org/about-cancer/treatment/drugs/mifamurtide.

Supporting Images Of Mifamurtide

A comparison of the difference between the cell wall of the two main types of bacteria: Gram-positive and Gram-negative. Amongst the key differences between them is the size of the cell wall made of peptidoglycan. Peptidoglycan is a chemical made of sugars and proteins. Gram-negative is more complex.

The signalling pathways involved in Mifarmitide.

Examples of chemotherapy for Ewing Sarcoma according to NCCN guidelines

Example one:

VDC/IE is recommended in accordance to the NCCN guidelines.

Primary chemotherapy treatment

VDC/IE is a multiagent chemotherapy consisting of Vincristine, Doxorubicin, Cyclophosphamide, and then alternating with Ifosfamide and Etoposide.

This can be taken for at least 9 weeks iA

Purpose: This is to decrease the tumour and achieve complete resection

Options for local control depend on age, tumour location, tumour size, response to chemotherapy, patient preference and anticipated morbidity.

1)Radiotherapy with chemotherapy can be used for local control.

2) Examples of surgery: wide excision, amputation in selected cases; adjuvant treatment can be given.

3) Chemotherapy post-surgery (adjuvant). This helps to minimise the risk of local recurrence after having curettage. This prevents the need for further surgery for resection and reconstruction.

Please visit the surgery on bone cancer section for further detail.

The duration or the length of time needed for chemotherapy after surgery like wide excision or amputation is between 28 and 49 weeks. This depends on the type of regimen and dosing schedule.

Examples of chemotherapy for relapsed cancers (returning cancers) according to NCCN guidelines

Clinical trials for new treatment

Example one

Vincristine, irinotecan, and temozolomide for relapsed or refractory Ewing sarcoma.

The overall response rate is 68%.

Example two

Irinotecan and topotecan with cyclophosphamide and temozolomide are linked with favourable response.

Example three

The CABONE trial, a multicenter, single-arm phase II trial, evaluated the activity of cabozantinib in patients with advanced Ewing sarcoma and osteosarcoma.

What is Cabozantinib?

This is a second-line treatment for patients with relapsed, refractory, or metastatic osteosarcoma.

It is an inhibitor of two main receptors: vascular endothelial growth factor receptor (VEGFR2) and the MET receptor.

The MET receptor signalling in non-cancerous conditions.

The tyrosine kinase receptor (MET) and its target substrate, Hepatocyte growth factor (HGF) are needed for growth and survival of cells in non-cancerous conditions.

The cells are found on the epithelial lining and migration of muscle progenitors (starting cells of muscles).

Other functions including to heal tissue damage and regenerating or making sites after healing in several organs.

MET receptor signalling and cancerous conditions

In cancerous conditions, MET stimulates the survival of cancer cells through production of new blood vessels that provide nutrients (angiogenesis), invasion, and facilitate the production of secondary cancers. They can also have mutated genetic lesions that maintain their gain of function in some primary tumours.

How does the MET signalling work?

The MET receptor binds to its target molecule and becomes activated via phosphorylation (the addition of phosphate groups).

They then interact with the GRB2-associated binding protein 1 (GAB1) Mult adaptor protein, to transduce the signal and recruit multiple proteins.

This causes the transcription of target genes for repair, growth and other cellular events.

The MET receptor also interacts with other molecules, e.g.

α6β4 integrin – to help with the downstream events in the signalling pathway

CD44 adhesion molecule – to help with the organisation of the cytoskeleton (the outer part of the cell)

The MET receptor also helps to support other signalling pathways, for instance, extracellular signal-regulated kinases (ERKs) and signal transducer and activator of transcription 3 (STAT3).

Supporting Images of Cabozantinib

What is the overall survival?

The overall survival (OS) was 84% at 6 months, 48% at 12 months and 14% at 24 months.

The median OS was 10.2 months and the median progression-free survival (PFS) of 4.4 months.

42% of patients had a metabolic tumour response, and it was well-tolerated in patients with advanced cancers. There were several side effects, e.g.

hypophosphatemia (low levels of phosphate in the blood)

high levels of the enzyme aspartate aminotransferase

palmar-plantar syndrome (hand-foot condition where skin is affected).

About Palmar-plantar syndrome

If one has a lighter skin tone, it becomes red. If there is a darker skin tone, areas become darker. The skin may also appear sore or painful or tingle or swell or peel or crack or blister.

Pneumothorax – air space in the pleural cavity near the lungs.

Neutropenia – low levels of neutrophils (type of white blood cells)

The difference between open and closed pneumothorax

The signs and symptoms in each grade of Palmar-Plantar syndrome

Chemotherapy For Osteosarcoma

First line of treatment

Cisplatin, Doxorubicin and High-dose methotrexate (MAP)

MAP is preferred in patients aged 40 years with excellent performance status.

Delayed elimination due to duct or renal impairment – a chemical called glucarpidase is strongly recommended in patients receiving high-dose methotrexate.

What is Glucarpidase?

Glucarpidase is a bacterial recombinant enzyme that prevents the kidneys from clearing methotrexate to maximise efficiency but lower toxicity level by hydrolysing it to inactive metabolites:

4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) and glutamate.

The liver undergoes detoxification

What other chemotherapeutic agents can be used to treat osteosarcoma for patients with non-metastatic resectable osteosarcoma?

Suggestion One

Cisplatin, doxorubicin, and methotrexate

Suggestion Two

Cisplatin, doxorubicin, methotrexate, and ifosfamide

Commentary on Suggestion One and Two:

Studies revealed there was no difference in the 6-year Event-Free Trial (EFS) which was 63 for Suggestion One and 64 for Suggestion Two.

However, their overall survival was different, 74 for Suggestion One and 70 for Suggestion Two.

Overall Survival (OS) is the time from diagnosis or the start of treatment until death from any cause.

Progression-Free Survival (PFS) is the time from the start of the treatment or randomization until disease progression or death from any cause, whichever occurs first.

Event-Free Survival is defined as the time from the start of treatment until the first presence of the predefined, negative clinical outcome (Event).

Suggestion Three: Gemcitabine

It can occur as a single agent: Gemcitabine (single agent)

a combined regimen either:

A) Docetaxel and Gemcitabine.

B) Cyclophosphamide and topotecan.

C) High dose methotrexate with or without etoposide and ifosfamide.

D) Ifosfamide, carboplatin and etoposide – This has been effective in treating replaced or refractory bone sarcoma.

What can be used for second line therapy for osteosarcoma?

A) Sofarenib

This is a type of targeted therapy, not chemotherapy.

The Progression Free Survival (PFS) at 4 months (primary endpoint) was 46%.

The Median Progression Free Survival was 4 months.

The Overall Survival was 7 months.

Chemotherapy For Adamantinoma

Surgery is best option and tend to nor respond to chemotherapy.

There is a change of being fully cured if all tumour cells are removed.

References

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Updated July 2026 Next Review July 2028