Chemotherapy and Targeted Therapy — MCQs
All are used for carcinoma head & neck except ?
What is the most important target of action of chlorambucil?
Many drugs are used as rescue therapy for preventing the adverse effects of anticancer drugs. Folinic acid is used in:-
Which of the following is the platinum-based chemotherapeutic agent used as first-line treatment for ovarian carcinoma?
Efalizumab disrupts the interaction between which of the following adhesion molecules?
What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
An elderly male presents with T3N0 laryngeal carcinoma. What would be the management?
Secukinumab is used in:
What is the most appropriate next step in management for a patient with a Stage III ovarian cancer with partial response to platinum-based chemotherapy?
Which of the following is not a cause of oropharyngeal carcinoma?
Chemotherapy and Targeted Therapy Indian Medical PG Practice Questions and MCQs
Question 1: All are used for carcinoma head & neck except ?
- A. 5FU
- B. Methotrexate
- C. Busulfan (Correct Answer)
- D. Cisplatin
Explanation: ***Busulfan*** - **Busulfan** is an **alkylating agent** primarily used in the treatment of **chronic myeloid leukemia (CML)** and as a conditioning regimen before bone marrow transplantation [2]. - It is not a standard chemotherapeutic agent used in the treatment of **head and neck squamous cell carcinoma**. *5FU* - **5-fluorouracil (5FU)** is a **pyrimidine analog** that inhibits DNA synthesis [1] and is a cornerstone in the treatment of **head and neck squamous cell carcinoma**, often used in combination with radiation or other chemotherapeutic agents. - It is particularly effective in **mucosal cancers** like those found in the head and neck. *Methotrexate* - **Methotrexate** is an **antimetabolite** that inhibits folate metabolism, leading to impaired DNA and RNA synthesis [1]. - It is widely used in the treatment of **head and neck cancers**, especially in recurrent or metastatic settings, and as a component of induction or palliative chemotherapy. *Cisplatin* - **Cisplatin** is a **platinum-based chemotherapy drug** that forms DNA adducts, leading to cell death. - It is considered one of the most active and commonly used agents in the treatment of **head and neck squamous cell carcinoma**, frequently given in combination with **radiation therapy** (chemoradiation) or other chemotherapy drugs.
Question 2: What is the most important target of action of chlorambucil?
- A. Myeloid tissue
- B. Neural tissue
- C. Skin
- D. Lymphoid tissue (Correct Answer)
Explanation: ***Lymphoid tissue*** - **Chlorambucil** is an **alkylating agent** primarily used in the treatment of various **lymphoproliferative disorders**. - Its main therapeutic effect is on rapidly proliferating cells, particularly those of **lymphoid origin**, such as in chronic lymphocytic leukemia (CLL) and other lymphomas. *Myeloid tissue* - While chlorambucil can have some effect on myeloid cells, it is not its primary or most important target; other drugs are more specifically used for **myeloproliferative disorders**. - Its use in conditions like chronic myeloid leukemia (CML) is limited and generally not first-line. *Neural tissue* - Chlorambucil is not primarily an agent targeting **neural tissue** and is not used in the treatment of neurological conditions. - It does not readily cross the **blood-brain barrier** to a significant extent, limiting its direct action on the central nervous system. *Skin* - Although some **lymphomas** can manifest with **cutaneous involvement**, chlorambucil's direct and most important target is not the skin itself but rather the underlying **lymphoid cells**. - It is not a primary treatment for general skin conditions or non-lymphomatous skin cancers.
Question 3: Many drugs are used as rescue therapy for preventing the adverse effects of anticancer drugs. Folinic acid is used in:-
- A. Cyclophosphamide toxicity
- B. Doxorubicin toxicity
- C. Methotrexate toxicity (Correct Answer)
- D. Cisplatin toxicity
Explanation: ***Methotrexate toxicity*** - **Folinic acid (leucovorin)** is a reduced folate that bypasses the metabolic block caused by **methotrexate** on dihydrofolate reductase. - It replenishes the body's **folate stores** and protects healthy cells from methotrexate's cytotoxic effects, particularly in the bone marrow and gastrointestinal tract. *Cyclophosphamide toxicity* - **Cyclophosphamide** toxicity, primarily hemorrhagic cystitis, is prevented by **mesna** (2-mercaptoethane sulfonate). - Mesna inactivates the urotoxic metabolite **acrolein** in the urine, preventing bladder damage. *Doxorubicin toxicity* - **Doxorubicin** causes cardiotoxicity, which can be mitigated by the iron-chelating agent **dexrazoxane**. - Dexrazoxane reduces the formation of **free radicals** that contribute to doxorubicin-induced myocardial damage. *Cisplatin toxicity* - **Cisplatin** toxicity, especially nephrotoxicity, is largely prevented by **aggressive hydration** and administration of **diuretics**. - **Amifostine** is another agent that can reduce cisplatin-induced nephrotoxicity, neurotoxicity, and ototoxicity by acting as a cytoprotectant.
Question 4: Which of the following is the platinum-based chemotherapeutic agent used as first-line treatment for ovarian carcinoma?
- A. Cyclophosphamide
- B. Methotrexate
- C. Cisplatin (Correct Answer)
- D. Dacarbazine
Explanation: ***Cisplatin*** - **Cisplatin** is a platinum-based chemotherapy drug that forms **DNA cross-links**, inhibiting DNA synthesis and leading to the death of rapidly dividing cells, making it highly effective against **ovarian carcinoma**. - It is a cornerstone of chemotherapy regimens for ovarian cancer, often used in combination with other agents such as paclitaxel. *Methotrexate* - **Methotrexate** is an **antimetabolite** that inhibits dihydrofolate reductase, thereby interfering with DNA synthesis. - While it is used in various cancers like leukemia, lymphoma, and some solid tumors (e.g., breast cancer, gestational trophoblastic disease), it is **not a primary recommended drug for ovarian carcinoma**. *Cyclophosphamide* - **Cyclophosphamide** is an **alkylating agent** that causes DNA damage, leading to cell death. - It is used in many cancers, including lymphoma, breast cancer, and some leukemias, but it is **not a first-line or primary agent for ovarian carcinoma** in contemporary treatment guidelines. *Dacarbazine* - **Dacarbazine** is an **alkylating agent** primarily used in the treatment of **malignant melanoma** and Hodgkin lymphoma. - It is **not indicated for the treatment of ovarian carcinoma**.
Question 5: Efalizumab disrupts the interaction between which of the following adhesion molecules?
- A. LFA-3 and ICAM-3
- B. LFA-1 and ICAM-1 (Correct Answer)
- C. LFA-3 and CD2
- D. LFA-3 and ICAM-1
Explanation: **LFA-1 and ICAM-1** - **Efalizumab** (now withdrawn) was a monoclonal antibody that targeted the **CD11a subunit of LFA-1**. - By binding to **LFA-1** on T-cells, efalizumab prevented its interaction with **ICAM-1** on endothelial cells and antigen-presenting cells, thereby inhibiting T-cell activation and migration. *LFA-3 and ICAM-3* - This interaction primarily involves **T-cell co-stimulation** (CD2 with LFA-3) and **adhesion** (ICAM-3 with LFA-1, though less prominent than ICAM-1). - Efalizumab's mechanism of action directly targeted **LFA-1/ICAM-1**, not this specific pair. *LFA-3 and CD2* - **CD2** on T-cells interacts with **LFA-3 (CD58)** on antigen-presenting cells, providing a **co-stimulatory signal** for T-cell activation. - While important for immune responses, this specific interaction was not the primary target of efalizumab. *LFA-3 and ICAM-1* - **LFA-3** (CD58) is a ligand for **CD2**, and **ICAM-1** is a ligand for **LFA-1**. They do not directly interact with each other in a functionally significant way that would be targeted by efalizumab. - Efalizumab targeted the **LFA-1/ICAM-1** pathway, not a combination involving LFA-3 with ICAM-1.
Question 6: What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
- A. Sorafenib
- B. Lapatinib (Correct Answer)
- C. Vemurafenib
- D. Erlotinib
Explanation: ***Lapatinib*** - Lapatinib is a **dual tyrosine kinase inhibitor** that targets both **HER-2** and **epidermal growth factor receptor (EGFR)**, acting as a **small molecule inhibitor** that binds to the intracellular domain of these receptors. - Unlike trastuzumab (a monoclonal antibody targeting the extracellular domain), Lapatinib's **intracellular mechanism of action** allows it to overcome common mechanisms of trastuzumab resistance, such as receptor truncation or masking of the extracellular epitope. - It is specifically approved for the treatment of **HER-2 positive metastatic breast cancer** in combination with capecitabine after progression on trastuzumab-containing regimens. *Sorafenib* - Sorafenib is a **multi-kinase inhibitor** primarily targeting RAF, VEGFR, and PDGFR, and is used in renal cell carcinoma and hepatocellular carcinoma. - It does not specifically target HER-2 and is **not indicated** for HER-2 positive trastuzumab-resistant breast cancer. *Vemurafenib* - Vemurafenib is a **BRAF inhibitor** used for treating BRAF V600E mutation-positive melanoma. - This drug has no direct indications or demonstrated efficacy for **HER-2 positive breast cancer** and does not address trastuzumab resistance mechanisms. *Erlotinib* - Erlotinib is an **EGFR tyrosine kinase inhibitor** primarily used for non-small cell lung cancer with activating EGFR mutations. - While it targets EGFR, it does **not effectively target HER-2** and lacks the dual inhibition necessary to overcome trastuzumab resistance in HER-2 positive breast cancer.
Question 7: An elderly male presents with T3N0 laryngeal carcinoma. What would be the management?
- A. Neoadjuvant chemotherapy followed by radiotherapy
- B. Radical radiotherapy followed by chemotherapy
- C. Radical radiotherapy without chemotherapy
- D. Concurrent chemoradiotherapy (Correct Answer)
Explanation: ***Concurrent chemoradiotherapy*** - For **T3 laryngeal carcinoma (moderately advanced)**, concurrent chemoradiotherapy is the preferred management to preserve the larynx while offering a good chance of cure. - This approach combines **radiation** with **chemotherapy** given at the same time to enhance the effect of radiation and improve local control. *Neoadjuvant chemotherapy followed by radiotherapy* - **Neoadjuvant chemotherapy** is typically reserved for more advanced (T4) or unresectable tumors to reduce tumor burden before definitive local treatment. - For T3 disease, concurrent chemoradiotherapy is generally preferred for organ preservation over sequential approaches. *Radical radiotherapy followed by chemotherapy* - Sequential treatment with **radiotherapy first** followed by chemotherapy is less effective than concurrent chemoradiotherapy for organ preservation and disease control in T3 laryngeal carcinoma. - This approach may be considered in specific cases, but it's not the primary recommendation for T3 laryngeal cancer. *Radical radiotherapy without chemotherapy* - While **radical radiotherapy alone** can be used for selected early-stage (T1-T2) laryngeal cancers, it is generally insufficient for T3 disease. - The addition of chemotherapy concurrently significantly improves outcomes for T3 larynx cancer compared to radiotherapy alone, by addressing microscopic disease and sensitizing tumor cells to radiation.
Question 8: Secukinumab is used in:
- A. Psoriasis (Correct Answer)
- B. Colorectal carcinoma
- C. Breast cancer
- D. Rheumatoid arthritis
Explanation: ***Psoriasis*** - **Secukinumab** is a monoclonal antibody that targets **interleukin-17A (IL-17A)**, a cytokine crucial in the pathogenesis of psoriasis. - It is approved for the treatment of **moderate to severe plaque psoriasis**, psoriatic arthritis, and ankylosing spondylitis. *Colorectal carcinoma* - **Secukinumab** is not used in the treatment of colorectal carcinoma; different classes of drugs like **chemotherapy**, **targeted therapies**, and **immunotherapy** (e.g., PD-1 inhibitors for MSI-high status) are employed. - Colorectal cancer treatment focuses on blocking pathways specific to cancer cell growth and survival, not IL-17A. *Breast cancer* - **Secukinumab** has no role in the treatment of breast cancer, which is managed with therapies such as **hormonal therapy**, **chemotherapy**, **HER2-targeted therapy**, and PARP inhibitors. - Breast cancer involves distinct molecular pathways and immune responses unrelated to IL-17A. *Rheumatoid arthritis* - While **rheumatoid arthritis** is an inflammatory condition, **secukinumab** is not a primary or approved treatment for it; other biologics like **TNF inhibitors**, **IL-6 inhibitors**, or **JAK inhibitors** are commonly used. - The inflammatory cascade in rheumatoid arthritis involves different key cytokines and cellular processes compared to those targeted by secukinumab.
Question 9: What is the most appropriate next step in management for a patient with a Stage III ovarian cancer with partial response to platinum-based chemotherapy?
- A. Bevacizumab
- B. Perform surgery (Correct Answer)
- C. Switch to radiotherapy
- D. Continue regimen
Explanation: ***Perform surgery (Interval Debulking Surgery)*** - In **Stage III ovarian cancer**, after an initial partial response to **platinum-based chemotherapy**, **interval debulking surgery** is the standard next step to remove residual disease. - This approach aims to reduce tumor burden to an optimal level (< 1 cm residual disease), which has been shown to improve overall survival in multiple trials (EORTC 55971, GOG-152). - Performed after 3-4 cycles of neoadjuvant chemotherapy when the patient has demonstrated response and is medically fit for surgery. *Bevacizumab* - **Bevacizumab** is an **anti-angiogenic agent** used in ovarian cancer, typically as part of frontline maintenance therapy or for recurrent disease, not as the immediate next step after partial response to primary chemotherapy when surgery is feasible. - While it can be incorporated into maintenance treatment post-surgery, it's not the primary next step after partial response when interval debulking surgery is indicated. *Switch to radiotherapy* - **Radiotherapy** has a limited role in the primary treatment of advanced ovarian cancer due to its widespread peritoneal nature. - It is sometimes used for localized recurrence or symptom palliation, but not as a standard next step after partial response to chemotherapy in Stage III disease. *Continue regimen* - Continuing the same regimen after only a **partial response** is generally not the most effective strategy when further tumor reduction via surgery is possible. - The goal in advanced ovarian cancer is **maximal cytoreduction**, and if residual disease is present after neoadjuvant chemotherapy, interval debulking surgery is preferred over continued chemotherapy alone.
Question 10: Which of the following is not a cause of oropharyngeal carcinoma?
- A. Occupational exposure to hydrochloric acid (Correct Answer)
- B. Smoking
- C. Human Papilloma Virus infection
- D. Occupational exposure to isopropyl oil
Explanation: **Explanation:** The primary risk factors for oropharyngeal carcinoma (OPC) are lifestyle-related and viral, rather than chemical or industrial. **1. Why Option A is the Correct Answer:** Occupational exposure to **hydrochloric acid (HCl)** is primarily associated with dental erosion and irritation of the upper respiratory tract, but it is **not** a recognized carcinogen for the oropharynx. In contrast, exposure to strong inorganic acid mists (like sulfuric acid) is linked specifically to **laryngeal cancer**, not oropharyngeal cancer. **2. Analysis of Other Options:** * **Smoking (Option B):** Tobacco use is a classic risk factor. Carcinogens like nitrosamines and polycyclic aromatic hydrocarbons cause field cancerization, leading to squamous cell carcinoma (SCC) of the entire aerodigestive tract. * **Human Papilloma Virus (Option C):** HPV (specifically **Type 16**) is now the leading cause of oropharyngeal cancer globally, especially involving the palatine tonsils and base of tongue. HPV-positive tumors have a better prognosis than tobacco-related ones. * **Isopropyl Oil (Option D):** Occupational exposure to the manufacture of isopropyl alcohol (specifically the "strong acid process" involving isopropyl oil) is a documented risk factor for cancers of the **paranasal sinuses and the oropharynx**. **Clinical Pearls for NEET-PG:** * **Most Common Site:** The **palatine tonsil** is the most common site for oropharyngeal SCC. * **HPV Marker:** **p16** immunohistochemistry is used as a surrogate marker for HPV-associated oropharyngeal cancer. * **Plummer-Vinson Syndrome:** Associated with post-cricoid (hypopharyngeal) carcinoma, not primarily oropharyngeal. * **Diet:** Deficiencies in Vitamin A and C are also implicated in the development of oral and pharyngeal malignancies.
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