Alkylating Agents Flashcards
What drugs are in the Alkylating Agents class?
Drugs in this class are:
- Cyclophosphamide
- lfosfamide
- Busulfan
- Melphalan
- Bendamustine
What is the brand name of Cyclophosphamide?
The brand name of this generic drug is:
- Cytoxan
What is the brand name of lfosfamide?
The brand name of this generic drug is:
- Ifex
What is the brand name of Busulfan?
The brand name of this generic drug is:
- Busulfex
- Myleran
What is the brand name of Melphalan?
The brand name of this generic drug is:
- Alkeran
- Evomela
What is the brand name of Bendamustine?
The brand name of this generic drug is:
- Belrapzo
- Bendeka
- Treanda
- Vivimusta
What is the generic of name of Cytoxan?
The generic name of this brand name drug is:
- Cyclophosphamide
What is the generic of name of Ifex?
The generic name of this brand name drug is:
- lfosfamide
What is the generic of name of Busulfex?
The generic name of this brand name drug is:
- Busulfan
What is the generic of name of Myleran?
The generic name of this brand name drug is:
- Busulfan
What is the generic of name of Alkeran?
The generic name of this brand name drug is:
- Melphalan
What is the generic of name of Evomela?
The generic name of this brand name drug is:
- Melphalan
What is the generic of name of Belrapzo?
The generic name of this brand name drug is:
- Bendamustine
What is the generic of name of Bendeka?
The generic name of this brand name drug is:
- Bendamustine
What is the generic of name of Treanda?
The generic name of this brand name drug is:
- Bendamustine
What is the generic of name of Vivimusta?
The generic name of this brand name drug is:
- Bendamustine
What are the main indications for use of Cyclophosphamide?
The main indications of this drug are:
- Non-Hodgkin lymphoma
- Hodgkin lymphoma
- Hematopoietic stem cell transplant
- Acute lymphoblastic leukemia
- Breast cancer
- Ewing sarcoma
- Graft-vs-host disease prophylaxis
- Multiple myeloma
- Osteosarcoma
- Rhabdomyosarcoma
- Small cell lung cancer
What are the main indications for use of lfosfamide?
The main indications of this drug are:
- Non-Hodgkin lymphoma
- Hodgkin lymphoma
- Ewing sarcoma
- Osteosarcoma
- Testicular cancer
- Bladder cancer
- Cervical cancer
- Ovarian cancer
- Soft tissue sarcoma
What are the main indications for use of Busulfan?
The main indications of this drug are:
- Hematopoietic stem cell transplant
- Polycythemia vera
- Essential thrombocythemia
What are the main indications for use of Melphalan?
The main indications of this drug are:
- Hematopoietic stem cell transplant
- Multiple myeloma
What are the main indications for use of Bendamustine?
The main indications of this drug are:
- Chronic lymphocytic leukemia
- Non-Hodgkin lymphoma
- Hodgkin lymphoma
What is the class and MOA of Cyclophosphamide?
This drug in the following class:
- Alkylating Agents
This drug’s MOA is as follows:
- Alkylates and cross-links DNA preventing DNA synthesis and cell division
What is the class and MOA of lfosfamide?
This drug in the following class:
- Alkylating Agents
This drug’s MOA is as follows:
- Alkylates and cross-links DNA preventing DNA synthesis and cell division
What is the class and MOA of Busulfan?
This drug in the following class:
- Alkylating Agents
This drug’s MOA is as follows:
- Alkylates and cross-links DNA preventing DNA synthesis and cell division
What is the class and MOA of Melphalan?
This drug in the following class:
- Alkylating Agents
This drug’s MOA is as follows:
- Alkylates and cross-links DNA preventing DNA synthesis and cell division
What is the class and MOA of Bendamustine?
This drug in the following class:
- Alkylating Agents
This drug’s MOA is as follows:
- Alkylates and cross-links DNA preventing DNA synthesis and cell division
What are the notable monitoring parameters for Cyclophosphamide?
The notable monitoring parameters for this drug are:
- Monitor for blood in urine (either through patient report or urine dipstick depending on protocol)
What are the notable monitoring parameters for lfosfamide?
The notable monitoring parameters for this drug are:
- Monitor for blood in urine (either through patient report or urine dipstick depending on protocol)
What are the notable monitoring parameters for Busulfan?
The notable monitoring parameters for this drug are:
- Monitor hepatic function for signs of veno-occlusive disease
- Monitor pharmacokinetics when giving high dose for stem cell transplant
What is the emetic potential of Cyclophosphamide?
The emetic potential of this drug is:
- High if >1500 mg/m2
- Moderate if <1500 mg/m2
What is the emetic potential of lfosfamide?
The emetic potential of this drug is:
- High if >2 g/m2
- Moderate if <2 g/m2
What is the emetic potential of Busulfan?
The emetic potential of this drug is:
- Moderate
What is the emetic potential of Melphalan?
The emetic potential of this drug is:
- High if >140 mg/m2
- Moderate if <140 mg/m2
What is the emetic potential of Bendamustine?
The emetic potential of this drug is:
- Moderate
Describe the emetic potential of the Alkylating Agents class.
The emetic potential of this drug class is:
- All are either moderate or high
What drugs in the Alkylating Agents class have a high emetic potential?
Drugs in the class with a high emetic potential are:
- Cyclophosphamide >1500 mg/m2
- Ifosfamide >2 g/m2
- Melphalan >140 mg/m2
What drugs in the Alkylating Agents class have a moderate emetic potential?
Drugs in the class with a moderate emetic potential are:
- Cyclophosphamide <1500 mg/m2
- Ifosfamide <2 g/m2
- Melphalan <140 mg/m2
- Busulfan
- Bendamustine
What drugs in the Alkylating Agents class have a low emetic potential?
Drugs in the class with a low emetic potential are:
- None (all are moderate or higher)
What drugs in the Alkylating Agents class have a minimal emetic potential?
Drugs in the class with a minimal emetic potential are:
- None (all are moderate or higher)
Describe the extravasation risk and management strategies for Bendamustine.
The extravasation risk and management strategies for this drug are as follows:
- Carries risk as it is an irritant with vesicant like properties.
- If extravasation occurs:
- Stop infusion
- Aspirate extravasated solution
- Elevate extremity
- Apply cold compress for 20 minutes 4 times daily
- Consider sodium thiosulfate (2 mL SQ for each mg of drug suspected to have extravasated)
Describe the extravasation risk and management strategies for the Alkylating Agents class.
The extravasation risk and management strategies for this drug class are as follows:
- Bendamustine carries extravasation risk as it is an irritant with vesicant like properties.
Describe the metabolism of the Alkylating Agents class.
The metabolism of this drug class is as follows:
- All agents are hepatically metabolized
- lfosfamide/cyclophosphamide are converted into active metabolites and acrolein
What is acrolein?
This metabolite is what cyclophosphamide and ifosfamide are converted into. It is toxic and causes bladder irritation and hemorrhagic cystitis.
Which alkylating agent(s) is most notable for causing mucositis (most common and most severe)?
Of the agents in this drug class, this ADR is most notable with melphalan.
What are the notable ADRs of melphalan?
The notable ADRs of this drug are:
- Mucositis ranging from mouth sores to irritation of the GI tract leading to severe diarrhea.
What are the notable ADRs of Ifosfamide?
The notable ADRs of this drug are:
- Hemorrhagic cystitis (irritation and bleeding of the bladder) due to accumulation of the toxic metabolite acrolein in the bladder.
- Rare cases of neurotoxicity (<15%) with symptoms developing hours to days after the dose (typical onset is 48-72 hours)
What are the notable ADRs of cyclophosphamide?
The notable ADRs of this drug are:
- Hemorrhagic cystitis (irritation and bleeding of the bladder) due to accumulation of the toxic metabolite acrolein in the bladder.
What are the notable ADRs of busulfan?
The notable ADRs of this drug are:
- Veno-occlusive disease (VOD)/Sinusoidal Obstructive Syndrome (SOS) (when used in high doses for bone marrow transplantation)
Which alkylating agent(s) is most notable for causing veno-occlusive disease?
Of the agents in this drug class, this ADR is most notable with busulfan (high dose as is used in stem cell transplant).
Which alkylating agent(s) is most notable for causing hemorrhagic cystitis?
Of the agents in this drug class, this ADR is most notable with cyclophosphamide and ifosfamide.
What are the notable/common ADRs of the Alkylating Agents class?
The notable/common ADRs of this drug class are:
- Mucositis
- Hemorrhagic cystitis
- Neurotoxicity
- Hepatic veno-occlusive disease/sinusoidal obstructive syndrome
Describe the strategy and rationale for management of mucositis caused by melphalan.
The strategy and rationale for management of this condition caused by this drug are:
- Oral mucositis can be prevented with cryotherapy. Due to short half-life, patients can chew on ice chips during and shortly after infusion causing vasoconstriction in the mouth and preventing chemotherapy from reaching the mucous membranes.
- GI mucositis is managed with anti-motility agents after ruling out infectious causes of diarrhea
Describe the strategy and rationale for management of hemorrhagic cystitis caused by alkylating agents (cyclophosphamide and ifosfamide).
The strategy and rationale for management of this condition caused by this drug are:
- Mesna is used as a chemoprotectant.
- Hemorrhagic cystitis is caused by accumulation of the toxic metabolite acrolein in the bladder.
- Mesna is oxidized to dimesna which in turn is reduced back to mesna in the kidneys supplying a free thiol group which binds and inactivates acrolein.
- Mesna is always given with ifosfamide and is often given with high dose cyclophosphamide.
- Mesna dose if typically 20% of the total daily ifosfamide/cyclophosphamide dose and is given for 3 doses
- Vigorous hydration is also used as both prevention and treatment of hemorrhagic cystitis.
- Additional treatments include bladder irrigation, hyperbaric oxygen, prostaglandin E2, and cystectomy for refractory cases.
Describe the strategy and rationale for management of neurotoxicity caused by ifosfamide.
The strategy and rationale for management of this condition caused by this drug are:
- Patients should monitor for S/Sx with a daily signature log.
- Symptoms generally resolve within 3 days of treatment discontinuation and can be managed with supportive care or methylene blue.
Describe the strategy and rationale for management of veno-occlusive disease (VOD) caused by busulfan.
The strategy and rationale for management of this condition caused by this drug are:
- Also called sinusoidal obstructive syndrome (SOS)
- Most commonly seen with high dose regimens use for stem cell conditioning
- Risk increases with higher areas under the curve
- Thus, pharmacokinetics measurements are often monitored, and doses are adjusted to target a specific AUC
- Patient should be monitored for hepatic dysfunction, unexplained weight gain, edema, abdominal pain, and jaundice
- Treatment options range from supportive care to defibrotide
Describe the half-life of drugs in the alkylating agents class.
The half-life of drugs in this class is described as follows:
- All are relatively short, ranging from 40 minutes with Bendamustine to 15 hours with ifosfamide
- This becomes especially important when managing adverse effects of melphalan with cryotherapy
Describe the history of alkylating agents.
The history of this drug class is as follows:
- These drugs were the first anti-cancer drugs and remain a cornerstone of anti-cancer therapy.
- The utility was discovered during World War I when researchers at Yale noticed that soldiers affected by mustard gas had low WBCs. They speculated that if mustard gas could destroy healthy WBCs, that it could destroy cancerous WBCs - this led to the use of alkylating agent as chemotherapy.
What is the frequency of emesis for an agent with a minimal emetic potential?
The frequency of emesis for an agent with this emetic potential is:
- <10%
What is the frequency of emesis for an agent with a low emetic potential?
The frequency of emesis for an agent with this emetic potential is:
- 10-30%
What is the frequency of emesis for an agent with a moderate emetic potential?
The frequency of emesis for an agent with this emetic potential is:
- 30-90%
What is the frequency of emesis for an agent with a high emetic potential?
The frequency of emesis for an agent with this emetic potential is:
- >90%
