SAM II Final Exam - Oncology Flashcards
T/F: Use of Doxorubicin is a prognosticator in cats with lymphoma
True
Better outcome in cats with doxorubicin use
If the standard of care is recommended to treat an osteosarcoma (curative intent), what is the expected cure rate (2 year survival)?
- 0-5%
- 5-10%
- 15-25%
- 30-40%
15-25%
________ is a neoplastic proliferation of hematopoietic stem cells in the bone marrow
leukemia
What chemotherapeutic drugs are affected by multidrug resistance?
vinca alkyloids, anthracyclines, actinomycin D
What lymph nodes typically experience the most dramatic enlargement in a case of multicentric lymphoma?
mandibular and superficial cervical
Diagnosis in these patients is usually very easy (fine needle aspirate), but it is important to immunophentype!
CD79a-positive stain. Is this a B cell or T cell lymphoma in this dog?
B cell lymphoma
B cells have a fair response to chemotherapy. Once these patients reach remission, it is usually a very durable remission and these patients have a much higher chance (than T cell) of being cured
What type of chemotherapeutic drug is Toceranib?
Tyrosine kinase inhibitor
After treatment with Doxorubricin, how many days should you wait to look for myelosupression?
7 days
What is a side effect of cyclophosphamide therapy caused by acrolein?
- Vesicant
- Sterile hemorrhagic cystitis
- Gastrointestinal toxicity
- Neurotoxicity
Sterile hemorrhagic cystitis
‘Petal’, the 12 year old FN Siamese presents with a mammary mass. What is the first thing you recommend?
- FNA
- Biopsy
- Radical bilateral, staged mastectomy
- Three thoracic radiographs
- Coagulation profile
Three thoracic radiographs
Some side-effects are specific to a particular chemotherapeutic agent or group of agents. Renal damage is most associated with what chemotherapeutic drug?
Cisplatin
Joey (who is a dog) has peripheral lymphadenopathy with a T-cell lymphoma but is otherwise healthy. Lymphoma cells are found in his spleen and liver with FNA but not in the bone marrow. The lymphoma is classified as a Multicentric, T cell, stage IV, substage A. You decide to treat Joey with a 19 week protocol.
He went into remission 1 month after starting CHOP, completed his 19 week protocol. 6 months later he relapsed. What rescue protocol would you use, and what is the expected RR and remission time?
- Doxorubicin, 70-90% RR, remission of 7-9 months
- Cyclophosphamide and Prednisolone combo, 60% RR, 3 months remission
- CCNU (Lomustine) or LOPP, 40% RR, 5 months remission time
CCNU (Lomustine) or LOPP, 40% RR, 5 months remission time
Some side-effects are specific to a particular chemotherapeutic agent or group of agents. Cardiomyopathy is most associated with what chemotherapeutic drug?
Doxorubicin
What drug may be used as a single agent protocol for multicentric lymphoma?
Doxorubicin
- 50-75% complete remission*
- Median survival of 6-8 months*
When staging an oral tumor, what would it mean to say a tumor is a T2a?
The tumor is 2-4 cm in diameter, without bone invasion
- T1: Tumor
- T2: Tumor 2-4 cm diameter
- T3: Tumor >4 cm diameter
- A: without bone invasion
- B: with bone invasion
T/F: Paraneoplastic syndromes often precede the onset of the primary cancer by weeks to months
True
T/F: This presentation is consistent with lymphadenitis
False
This presentation is consistent with _lymphoma_. Note the homogenous population of lymphoblasts (~3-5x the size of RBCs) occupying more than 50% of the cell population
Lymphadenitis would be characterized by a large population of neutrophils
Joey (who is a dog) has peripheral lymphadenopathy with a T-cell lymphoma but is otherwise healthy. Lymphoma cells are found in his spleen and liver with FNA but not in the bone marrow. The lymphoma is classified as a Multicentric, T cell, stage IV, substage A.
When we consider Joey’s lymphoma, which is a negative prognosticator?
- Stage
- Location (multicentric)
- Immunophenotype (T cell)
- Grade
Immunophenotype (T cell)
T/F: Mediastinal lymphoma is most common in younger FIV-positive cats
False
Mediastinal lymphoma is most common in younger _FeLV-positive_ cats
The most commonly used chemotherapeutic drug associated with thrombocytopenia is:
lomustine (CCNU®)
If this toxicity occurs, you MUST stop using the drug
T/F: Oral melanoma may be treated by vaccination
True
- Canine melanoma vaccine - fully licensed for Stage II and III oral melanoma
- Sensitize the dog to Tumor Associated Antigen (TAA) – unique or a mutation
- Xenogeneic DNA vaccine - tyrosinase
-
Dosage
- 0.4 mL dose administered with the Canine Transdermal Device
- Injection site: muscles of the medial thigh just caudal to the femur
- Initial treatment: 4 doses of vaccine at two week intervals
- Booster dose at six month intervals
Refer to the images below. What is the correct criticism for this chemotherapy administration protocol?
- No mask, eye shield, double gloving (nitrile) gloves used
- A catheter does not necessarily need to be placed for Vincristine
- The vet should not be smiling, cancer is serious business
- I don’t see a Phaseal system in place
No mask, eye shield, double gloving (nitrile) gloves used
In dogs, Stage ___ lymphoma is characterized by generalized lymph node involvement
In dogs, Stage III lymphoma is characterized by generalized lymph node involvement
It is important to check hematology prior to chemotherapy and 7 days post-chemotherapy, except when using __________ or __________, which both have a severe delay in the myelosuppressive effect (so we’ll check them 2-3 weeks post-chemo).
It is important to check hematology prior to chemotherapy and 7 days post-chemotherapy, except when using carboplatin or lomustine, which both have a severe delay in the myelosuppressive effect (so we’ll check them 2-3 weeks post-chemo).
Refer to the diagram and indicate at what point CT/MR would be able to detect cancer:
B
Joey (who is a dog) has peripheral lymphadenopathy with a T-cell lymphoma but is otherwise healthy. Lymphoma cells are found in his spleen and liver with FNA but not in the bone marrow. The lymphoma is classified as a Multicentric, T cell, stage IV, substage A.
What treatment would you recommend for Joey if the owner elects curative intent?
- Prednisolone
- Single agent CCNU
- Single agent Doxorubicin
- Multi-agent COP
- Current CHOP (19 week protocol)
Current CHOP (19 week protocol)
T/F: The majority of mammary gland tumors in cats are malignant
True
In cats, MGTs have a tendency to move into the lungs and are associated with high prevalence of developing pleural effusion. We don’t really even biopsy mammary tumors in cats… we just cut them out.
T/F: The use of TMS for 14 days post-doxorubicin markedly reduces the likelihood of needing gastrointestinal antibiotics
True
T/F: Alopecia is the most common side effect associated with chemotherapeutic agents
False
Gastrointestinal effects account for the majority of the side effects
- Anorexia, vomiting, diarrhea, colitis
- Direct effect on gut lining
- Pancreatitis (L-asparaginase)
- Central effect (CTZ) (Cisplatin)
In cats, presentation can be similar for inflammatory bowel disease (IBD) and alimentary lymphoma. Because veterinarians have racked up some sort of good karma throughout the years, the treatment for both of these conditions is essentially the same! Woo!
What is the treatment?
Chlorambucil and prednisolone
What chemotherapeutic agent MUST be included in any chemotherapy protocol for hemangiosarcoma?
Doxorubicin
Note: there doesn’t seem to be much difference in whether Doxorubicin is used alone or as part of a multi-agent therapy
8 year old Golden Retreiver with generalized lymphadenopathy. On FNA, this is what you see.
What is your diagnosis?
lymphoma
There are >50% blasts (consistent with lymphoma). The best treatment for this dog would likely be chemotherapy
Which is correct regarding feline intestinal lymphoma?
- The most common form is high grade, lymphoblastic
- Mostly FeLV positive
- Young siamese are predisposed
- Characterized by diffuse thickening of the muscularis propria on ultrasonography
Characterized by diffuse thickening of the muscularis propria on ultrasonography
T/F: If your patient has normal PTHrp levels, you’re able to easily rule out malignant cancer
False
Normal PTHrp DOES NOT RULE OUT CANCER
What dog breeds are predisposed to developing mammary gland tumors?
poodles, dachshunds, spaniels
What method of administration is NOT associated with reduced risk of the sterile hemorrhagic cystitis (as the result of acrolein toxicity)?
- Divided doses orally over three days
- Administration of Mesna at the same time as IV drug
- Administration of Furosemide period to Cyclophosphamide
- Giving the drug at night
- Salty snacks to encourage drinking
Giving the drug at night
In dogs, Stage ___ lymphoma is characterized by liver and spleen involvement
In dogs, Stage IV lymphoma is characterized by liver and spleen involvement
Nasal lymphoma can often mimic nasal adenocarcinoma. One big difference is sensitivity to radiotherapy. Which tumor type is sensitive to radiotherapy?
lymphoma
Joey (who is a dog) comes to your clinic for a 7 day follow-up check post-cyclophosphamide (CHOP). He is due to receive vincristine. His neutrophil count is 1200 cells/uL (1.2.10^9/L: >3.10^9/L). What do you suggest to Joey’s owner?
- Give the vincristine, but at a 25% reduced dose
- Substitute with a non-myelotoxic drug
- Postpone chemotherapy for 7 days and prescribe antibiotics (TMS)
- Stop chemotherapy altogether
Postpone chemotherapy for 7 days and prescribe antibiotics (TMS)
Anaplastic carcinoma tends to infect the ________ mammary glands in dogs
inguinal (5th set of mammary glands)
Anaplastic carcinomas are highly aggressive and nasty, but only make up ~4%
There are really only two instances in which we utilize bone marrow biopsy in the diagnosis of lymphoma. What are they?
- If we see cytopenias
-
If there is an extranodal lymphoma and we think surgery alone could cure
- (want to be sure there is no cancer anywhere else)
With regard to cancer treatment, what does it mean in veterinary medicine for an animal to be ‘cured’?
Two years of remission while not receiving chemotherapy
In a general sense, what type of tumor is present in this patient?
carcinoma
________ is the most common metastatic intracranial neoplasm
hemangiosarcoma
mechanism of metastasis is hematogenous
How many radiographic views should be taken to assess tumor metastasis?
Three
right lateral, left lateral, and dorsoventral views
Pilot, 14 yr, MN, Chow presents with an ulcerated, swollen mass on the muzzle. FNA confirms it is a MCT. The owner decides that she would like to proceed with definitive treatment for the MCT. The grade is Patnaik III, or grade II on the 2-tiered system, c-kit PCR positive. What treatment do you recommend after staging?
- Radiation: LINAC
- Chemotherapy: CCNU & Vinblastine
- Chemotherapy: Masivet
- Surgery/radiation for locoregional control and chemotherapy for distant (L and M) and long-term Masivet
Surgery/radiation for locoregional control and chemotherapy for distant (L and M) and long-term Masivet
Masitinib (Masivet®) is a tyrosine kinase inhibitor
Some side-effects are specific to a particular chemotherapeutic agent or group of agents. Cystitis is most associated with what chemotherapeutic drug?
Cyclophosphamide
What is the highest predictor for a dog developing osteosarcoma?
wither height (size of the dog)
- The bigger the dog, the higher the chance of developing osteosarcoma*
- Exceptions: Poodles and Pekingese are also at high risk of developing osteosarcoma*
Pilot, 14 yr, MN, Chow presents with an ulcerated, swollen mass on the muzzle. FNA confirms it is a MCT. The owner has very limited funds. What is the best option for him?
- Curative intent - surgery, radiation, and vinblastine/CCNU
- TKI - Toceranib
- Palliative steroid therapy with H1 and H2 blockers
- NSAID and tramadol
- Doxorubicin single agent chemotherapy
Palliative steroid therapy with H1 and H2 blockers
T/F: Alimentary lymphoma is most commonly seen in dogs
False
- Alimentary lymphoma is most commonly seen in cats*
- Full thickness biopsy is the best technique for diagnosis*
T/F: The majority of mammary gland tumors in dogs are malignant
False
Mammary gland tumors in dogs are ~50% benign, ~50% malignant
When staging an oral tumor, what would it mean to say a tumor is a T3b?
The tumor is >4 cm in diameter, with bone invasion
- T1: Tumor <2 cm diameter
- T2: Tumor 2-4 cm diameter
- T3: Tumor >4 cm diameter
- A: without bone invasion
- B: with bone invasion
T/F: Biopsy is almost always indicated for feline mammary gland tumors
False
~90% of feline mammary gland tumors are malignant - don’t need to biopsy
T/F: Nasal squamous cell carcinoma in dogs and cats is very sensitive to radiotherapy
False
Nasal squamous cell carcinoma in cats is very sensitive to radiotherapy. Not in dogs.
T/F: The majority of lymphomas in canines are multicentric
True
80-85% of lymphomas in dogs are multicentric
What PCR test can provide information about whether a lymphoma is monoclonal or polyclonal?
PARR
_P_CR for _a_ntigen _r_eceptor _r_earrangement
-
Helpful for differentiating monoclonal vs. polyclonal
- Benign - polyclonal
- Malignant - monoclonal
- Can monitor for cellular remission (residual disease)
- Ideal for relapse, pleural fluid, and bone marrow
When is it recommended to give recombinant granulocyte colony stimulating factor (rG-CSF)?
if you’ve accidentally and severely overdosed your patient
and you know that in 7-10 days time there will be a massive myelosuppression
Vincristine and Vinblastine are specific to what phase of the cell cycle?
Mitosis
- Vincristine and Vinblastine are plant alkaloids*
- The benefit of knowing this is that you can predict when the maximum side effects will occur. So if you know that a drug works in a specific stage of the cycle, toxicity to the host will predictably occur ~7 days after.*
________ is the most common form of cutaneous neoplasia in the dog
mast cell tumor (MCT)
What type of chemotherapeutic drug is cyclophosphamide?
alkylating agent
creates cross-linked DNA with strand breaks
Joey, 6 yo, MN Golden Retreiver is diagnosed with an osteosarcoma. The owner wants curative intent. What are your treatment recommendations?
- Start him on chemotherapy only
- Amputate the limb or limb sparing surgery
- Amputation/limb sparing + chemotherapy combination
- Radiation therapy of the sarcoma - stereostatic “gamma knife”
- Pain killer including biphosphonates - it is a poor prognosis
Amputation/limb sparing + chemotherapy combination
What class of chemotherapeutics are most often used as rescue drugs?
Alkylating agents
They don’t have cross-reactivity with MDR resistance
________ is the most common clinical sign associated with multiple myeloma
anemia
The __________ refers to the proportion of proliferating cells within a tumor
growth fraction (GF)
What is anatomical staging of a tumor?
Defining the anatomical extent of the tumor in terms of primary site and distant spread
What is the term to describe a neoplasm associated alteration in bodily structure or function that occurs distant to a tumor?
paraneoplastic syndrome
parallels the underling malignancy, with resolution of paraneoplastic syndrome after successful treatment of the tumor
T/F: Elevated ALKP is associated with a poorer prognosis in dogs with osteosarcoma
True
What is the most common site of origin for hemangiosarcomas?
spleen (50%)
T/F: Alkylating agents and anti-tumor antibiotics are cell cycle non-specific
True
Because of this, it can be difficult to predict when the maximum side effects will occur.
How do you definitively differentiate between lymphoma and acute leukemia?
bone marrow aspirate
- Acute leukemia will have more than 30-40% lymphoblasts in the bone marrow. Lymphoma will have less than 30% lymphoblasts.*
- In addition to bone marrow aspirate, there will be a much more pronounced lymphadenopathy with lymphomas. Splenomegaly will be seen with acute leukemia
T/F: The majority of splenic masses are malignant and the majority of malignancies are hemangiosarcomas
True
2/3 of splenic masses are malignant and 2/3 of malignancies are hemangiosarcomas
Joey (who is a dog) comes to your clinic for a 7 day follow up check post-doxorubicin (CHOP). His neutrophil count is 300 cells/uL and he has a fever. What do you suggest to Joey’s owner?
- Recommend repeat sampling in 7 days to see if he has recovered from his nadir
- Substitute doxorubicin in the future with dactinomycin
- Send Joey home with TMS for a course of antibiotics
- Admit Joey to the isolation facility and start with broad spectrum antibiotics
Admit Joey to the isolation facility and start with broad spectrum antibiotics
In a general sense, what type of tumor is present in this patient?
round cell tumor
If your patient is still persistently hypoglycemic after surgery, what is the drug of choice for medical management?
Diazoxide
- Prevents the release of insulin into circulation
- Very expensive and usually requires a compounding pharmacist for formulation
Joey has peripheral lymphadenopathy with a T-cell lymphoma but is otherwise healthy. Lymphoma cells are found in his spleen and liver with FNA but not in the bone marrow. The lymphoma is classified as a Multicentric, T cell, stage IV, substage A.
What is the estimated response rate and remission time if we treated Joey with a 19 week protocol?
- 30%, 3 months
- 60%, 6 months
- 80%, 12 months
- 90%, 2 years
80%, 12 months
Joey has peripheral lymphadenopathy with a T-cell lymphoma but is otherwise healthy. Lymphoma cells are found in his spleen and liver with FNA but not in the bone marrow. The lymphoma is classified as a Multicentric, T cell, stage IV, substage A. You decide to treat Joey with a 19 week protocol.
He relapses in the middle of his 19 week CHOP protocol. What do you recommend?
- Reinduce with CHOP, week 1
- CCNU
- Prednisolone
- Euthanize
Reinduce with CHOP, week 1
The chemotherapeutic agent of choice for transmissible venereal tumor (TVT) is:
Vincristine
T/F: Prednisolone may be indicated in the treatment of hypercalcemia
True
but ONLY after you have ruled out the possibility of cancer. You will forever mask the cancer if you give prednisolone and you haven’t diagnosed it. Also , if the patient has lymphoma and you give prednisolone, you will worsen the prognosis because the patient will be more likely to be resistant to chemotherapy
T/F: The majority of patients with lymphoma are asymptomatic
True
What is the most important prognosticator for lymphoma in the dog?
substage
- Substage a: no systemic signs
- Substage b: systemic signs**
Prognosis is much worse for dogs showing clinical signs. These patients do not do as well with chemotherapy and have a predictably shorter mean survival time
‘Petal’, the 12 year old FN Siamese presents with a mammary mass. Petal’s MGT: single, left cranial thoracic MG mass, 4.7 cm diameter, LNN normal size. What is the correct negative prognosticator?
- Size: >4 cm is bad
- Tumor type: sarcoma vs. carcinoma
- MG location: thoracic good
- Only one mass - good
- N0 - good
Size: >4 cm is bad
T/F: There is no difference in outcome in cats between T cell and B cell lymphoma
True
T/F: The presence of cancer cachexia is a negative prognosticator
True
-
Cancer cachexia: weight loss and metabolic alterations observed despite adequate nutritional intake
- (whereas alterations observed due to poor nutritional intake is termed cancer anorexia)
The chemotherapeutic agent of choice for mast cell tumors and relapse lymphoma is:
Lomustine (CCNU®)
Lomustine is an alkylating agent
The chemotherapeutic of choice for multiple myeloma is:
Melphalan
- Melphalan is an alkylating agent*
- Treatment for multiple myeloma involves Melphalan and prednisone*
T/F: When using an emetogen (Cisplatin), it is recommended to withhold food on the morning of chemo treatment
True
This will help to avoid food aversion
Which is an example of a paraneoplastic syndrome?
- Peripheral neuropathy due to vincristine
- Microcytic hypochromic anemia in a cat from intestinal MCT
- Microcytic hypochromic anemia in a dog due to dermal MCT
- Thrombocytopenia due to a splenic hemangiosarcoma
Microcytic hypochromic anemia in a dog due to dermal MCT
In terms of predicting outcome with mast cell tumors, the most important aspect of staging is:
lymph node evaluation (FNA or biopsy)
What is the main treatment for mammary tumors?
SURGERY
Chemotherapy and endocrine therapy is unproven
T/F: Ovariohysterectomy does not play a role in the development of mammary tumors
False
- Ovariohysterectomy does play a role in the development of mammary tumors. Ovariohysterectomy can reduce risk in both cats and dogs*
- Note, however, that if you’re surgically removing a mammary gland tumor, performing OVH concurrently has no effect on progression of malignant tumors, time to metastasis, or overall survival*
What is the general guideline for osteosarcoma predilection sites?
away from the elbows, toward the knees
distal radius is most common (except in small dogs, where the femur is most common). The site with the worst prognosis is the proximal humerus (one of the rarest locations)
What is the expected MST in a dog that has had a splenectomy for hemoabdomen but no follow-up chemotherapy?
- 3 weeks - 3 months
- 3 months - 6 months
- 6 months - 12 months
- 2 years
3 weeks - 3 months
How do you differentiate acute vs. chronic leukemia?
-
Acute: Neoplastic transformation early in the cell lineage (proliferation of blasts)
- Easier to diagnose (it’s not normal to see lymphoblasts in circulation)
- Poor prognosis
-
Chronic: Neoplastic transformation late in the cell lineage (proliferation of mature cells)
- The distinguishing characteristic for chronic leukemia is a massive lymphocytosis
- Good prognosis
What is not a prognosticator for OSA in a dog?
- Age, >7 year is worse
- Location, proximal humerus is worse
- ALKP, failure to decline to normal by D40 is worse
- Metastasis, presence has a shorter MST
Age, >7 year is worse
What is a specific hematological feature of hemangiosarcoma?
- Anemia
- Heinz bodies
- Schistocytes
- Spherocytes
- Hypochromic RBC
Schistocytes
What therapeutic agents are registered for c-kit positive mast cell tumors?
Masitinib/Toceranib
Tyrosine kinase inhibitors
What type of chemotherapeutic drug is carboplatin?
platinum compound
mechanism is similar to alkylating agents (cross-link DNA)
What is the chemotherapeutic agent of choice for treatment of hypoglycemia?
Streptozocin
- Islet cell specific chemotherapy
- Typically used in conjunction with surgery for best prognosis.
- Remember that this drug is associated with nephrotoxicity, so it requires diuresis beforehand
What is NOT a clinical complication of a multiple myeloma?
- CVA (Cerebrovascular accident)
- Retinal detachment
- CKD
- Hypertrophic cardiomyopathy
- Hypercalcemia
- Thromboembolism
Thromboembolism
T/F: When chemotherapy and amputation are combined, we can acheive curative intent in patients with osteosarcoma
True
~20% of dogs treated with amputation + chemotherapy survive past 24 months (curative)
CD3-positive stain. Is this a B cell or T cell lymphoma in this dog?
T cell lymphoma
T cell lymphomas MAY respond to chemotherapy, but they usually develop a relapse very quickly and they have a very short clinical remission
You recheck a Pug you referred for radiation therapy (LINAC) for a muzzle MCT after the second week. What is the correct assessment?
- The dramatic response is a good sign
- Too early to make a decision, the tumor may recur
- This is a highly aggressive tumor and carries a grave prognosis
- The cancer is cured… go home, Pug
Too early to make a decision, the tumor may recur
Depigmented nose with bilateral discharge. What is your diagnosis?
aspergillosis
Joey has peripheral lymphadenopathy with a T-cell lymphoma but is otherwise healthy. Lymphoma cells are found in his spleen and liver with FNA but not in the bone marrow. Classify this lymphoma:
- Multicentric ,T cell, stage IV, substage A
- Multicentric, T cell, stage V, substage A
- Multicentric, T cell, stage IV, substage b
- Extranodal lymphoma
- Acute lymphocytic leukemia
Multicentric, T cell, stage IV, substage A
Gastroduodenal ulcers are due to an excess amount of ________ in MCTs (a negative prognosticator) or ________ in gastrinomas
Gastroduodenal ulcers are due to an excess amount of histamine in MCTs (a negative prognosticator) or gastrin in gastrinomas
What cat breed is predisposed to developing mammary gland tumors?
Siamese
T/F: Radiotherapy can provide definitive treatment for osteosarcomas
False
Osteosarcomas are radioresistant. Radiotherapy would be used for palliative treatment only
Some side-effects are specific to a particular chemotherapeutic agent or group of agents. Neuropathy is most associated with what chemotherapeutic drug?
Vincristine
T/F: Multiple myeloma is associated with polyclonal gammopathy
False
Multiple myeloma is associated with _monoclonal gammopathy_ (“finger of death”)
A dog receives 6 Gy of radiation weekly for 4 weeks, weekly, before chemotherapy for an osteosarcoma. There is no amputation. Describe the type of radiation course:
- Definitive, hypofractionated, adjuvant
- Definitive, hyperfractionated, adjuvant
- Palliative, hypofractionated, neoadjuvant
- Palliative, hyperfractionated, adjuvant
Palliative, hypofractionated, neoadjuvant
What platinum compound is known to cause fatal pulmonary edema in cats?
Cisplatin
“Cisplatin splats cats”
T/F: Alkylating agents and Carboplatin are not affected by multidrug resistance
True
Alkylating agents (Melphalan, Lomustine) and Carboplatin are not affected by multidrug resistance
