A 64-year-old woman comes to the physician for her routine health maintenance examination. She feels well. She had cervical cancer and received radiotherapy 8 years ago. Her vital signs are within normal limits. On percussion, the spleen size is 15 cm. Otherwise, the physical examination shows no abnormalities. The laboratory test results are as follows: Hemoglobin 10 g/dL Mean corpuscular volume 88 μm3 Leukocyte count 65,000/mm3 Platelet count 500,000/mm3 Two images of the peripheral blood smear are shown on the image. Which of the following is the most appropriate next step in management?

Allogeneic stem cell transplantation

A 54-year-old woman is diagnosed with locally-advanced invasive ductal carcinoma of the breast. She undergoes surgical resection, radiation therapy, and is now being started on adjunctive chemotherapy with cyclophosphamide and doxorubicin. The patient is scheduled for follow up by her primary care provider. Which of the following tests should be performed regularly to monitor her current treatment regimen?

No regular monitoring indicated

A 57-year-old man presents to his oncologist to discuss management of small cell lung cancer. The patient is a lifelong smoker and was diagnosed with cancer 1 week ago. The patient states that the cancer was his fault for smoking and that there is "no hope now." He seems disinterested in discussing the treatment options and making a plan for treatment and followup. The patient says "he does not want any treatment" for his condition. Which of the following is the most appropriate response from the physician?

"It must be very challenging having received this diagnosis. I want to work with you to create a plan."

"You seem upset at the news of this diagnosis. I want you to go home and discuss this with your loved ones and come back when you feel ready to make a plan together for your care."

"It must be tough having received this diagnosis; however, new cancer therapies show increased efficacy and excellent outcomes."

"We are going to need to treat your lung cancer. I am here to help you throughout the process."

"I respect your decision and we will not administer any treatment. Let me know if I can help in any way."

A 64-year-old woman comes to the physician because of a 7-month history of abdominal discomfort, fatigue, and a 6.8-kg (15-lb) weight loss. Physical examination shows generalized pallor and splenomegaly. Laboratory studies show anemia with pronounced leukocytosis and thrombocytosis. Cytogenetic analysis shows a BCR-ABL fusion gene. A drug with which of the following mechanisms of action is most appropriate for this patient?

Ribonucleotide reductase inhibitor

A 72-year-old man has been recently diagnosed with stage 3 squamous cell carcinoma of the oral cavity. After the necessary laboratory workup, concurrent chemoradiation therapy has been planned. Radiation therapy is planned to take place over 7 weeks and he will receive radiation doses daily, Monday–Friday, in 2.0 Gy fractions. For concurrent chemotherapy, he will receive intravenous cisplatin at a dosage of 50 mg/m2 weekly for 7 weeks. Which of the following best explains the mechanism of action of the antineoplastic drug that the patient will receive?

Formation of interstrand DNA cross-links

Free radical-mediated lipid peroxidation

Inhibition of polymerization of tubulin

A 71-year-old woman presents to her hematologist-oncologist for follow up after having begun doxorubicin and cyclophosphamide in addition to radiation therapy for the treatment of her stage 3 breast cancer. Her past medical history is significant for preeclampsia, hypertension, polycystic ovarian syndrome, and hypercholesterolemia. She currently smokes 1 pack of cigarettes per day, drinks a glass of wine per day, and denies any illicit drug use. The vital signs include: temperature 36.7°C (98.0°F), blood pressure 126/74 mm Hg, heart rate 111/min, and respiratory rate 23/min. On physical examination, the pulses are strong and irregular, she has a grade 3/6 holosystolic murmur heard best at the left upper sternal border, clear bilateral breath sounds, and erythema over her site of radiation. Which of the following statements regarding doxorubicin is true?

Doxorubicin has a maximum lifetime dose, due to the risk of cardiac toxicity

Doxorubicin has a maximum lifetime dose, due to the risk of pulmonary toxicity

Doxorubicin will increase her risk for deep vein thrombosis (DVT) and pulmonary embolism (PE)

Doxorubicin frequently causes an acneiform rash

Doxorubicin frequently causes cystitis

Antineoplastic combination regimens for USMLE Step 2 CK: High-Yield Pharmacology Lessons

Combination Principles - Why More is More

Maximize Efficacy: Achieve synergistic cytotoxicity ($1+1>2$) by targeting different molecular pathways and cell cycle phases.
Broaden Coverage: Effective against heterogeneous cancer cell populations, including both rapidly dividing and quiescent cells.
Prevent/Overcome Resistance: Reduces the probability of resistant clones emerging by attacking the cancer from multiple angles.
Minimize Toxicity: Combine drugs with non-overlapping dose-limiting toxicities (e.g., avoid combining two drugs that both cause severe bone marrow suppression).

Timeline of Combination Therapy Development

⭐ The MOPP regimen (Mechlorethamine, Oncovin, Procarbazine, Prednisone) for Hodgkin lymphoma was one of the first successful combination therapies, dramatically improving cure rates from <10% to >70%.

📌 Many regimens are acronyms, e.g., R-CHOP for lymphoma: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone.

Heme Malignancy Regimens - Alphabet Soup Assault

📌 Mnemonic: Key drugs are often represented by their first letter in the regimen acronym.

Malignancy	Regimen	Key Components
Hodgkin Lymphoma	ABVD	Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine
Non-Hodgkin (DLBCL)	R-CHOP	Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone
CLL/SLL	FCR	Fludarabine, Cyclophosphamide, Rituximab
AML	7 + 3	Cytarabine (for 7 days) + Idarubicin/Daunorubicin (for 3 days)
Multiple Myeloma	VRd	Velcade (Bortezomib), Revlimid (Lenalidomide), dexamethasone

Solid Tumor Regimens - Targeted Cocktail Party

Regimen Combination	Target(s) & Synergy	Key Indication(s)
Dabrafenib + Trametinib	BRAF V600E + MEK; Vertical pathway blockade	Metastatic Melanoma
Trastuzumab + Pertuzumab	HER2 (dual blockade); Prevents dimerization	HER2+ Breast Cancer
Ipilimumab + Nivolumab	CTLA-4 + PD-1; Synergistic immune activation	Melanoma, RCC, NSCLC
Atezolizumab + Bevacizumab	PD-L1 + VEGF; Enhances T-cell tumor infiltration	Hepatocellular Carcinoma, NSCLC
Pembrolizumab + Lenvatinib	PD-1 + Multi-kinase (VEGFR); Immune + anti-angiogenic	Endometrial Ca, RCC

Toxicity & Rescue - The Damage Control

Drug / Toxin	Specific Toxicity	Rescue Agent / Management
Methotrexate	Myelosuppression, Mucositis	Leucovorin (Folinic Acid) "rescue"
Cisplatin	Nephrotoxicity, Ototoxicity	Amifostine, Chloride Diuresis
Doxorubicin	Dilated Cardiomyopathy	Dexrazoxane (Iron Chelator)
Cyclophosphamide	Hemorrhagic Cystitis (Acrolein)	Mesna, Aggressive Hydration
Bleomycin	Pulmonary Fibrosis, Skin changes	Monitor PFTs, Corticosteroids
Vinca Alkaloids	Peripheral Neuropathy (dose-limiting)	Dose modification/discontinuation

Acrolein inactivation in bladder and liver

High‑Yield Points - ⚡ Biggest Takeaways

Combination chemotherapy regimens like ABVD or R-CHOP are standard to maximize efficacy and prevent drug resistance.

Drugs are selected to have synergistic effects by targeting different cellular mechanisms or cell cycle phases.

A key principle is combining agents with non-overlapping toxicities to improve patient tolerance and allow for higher doses.

Leucovorin is used for "rescue" with high-dose methotrexate but potentiates 5-FU's cytotoxicity.

Always monitor for cumulative, dose-limiting toxicities like doxorubicin cardiotoxicity or bleomycin pulmonary fibrosis.

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play