Radiosensitizers InSquamous Cell Carcinoma Of Head and Neck
Amr Ahmed Al-Sayed Ali;
Abstract
HNC comprises a diverse group of tumor types arising from the upper aerodigestive tract, including the lip, nasal and oral cavities, sinuses, pharynx, larynx, and other sites in this anatomical region.
Head and neck cancer is the fifth most common cancer worldwide, with an estimated annual global incidence of approximately 600,000 cases.
The vast majority of HNC diagnoses (>90%) are of squamous epithelial cell origin and are thus termed head and neck squamous cell carcinomas (HNSCC).
Main risk factors of HNSCC includes smoking, alcohol, chewing tobacco, viral infection, genetic tendency, previous history of head or neck cancer, history of cancer in first-degree family members, exposure to radiation, nutritional disorders, and poor oral hygiene.
HNC treatment is complex and depends on the anatomical location of the tumor and involvement of adjacent organs. The major challenge in treating HNC is obtaining a high cure rate while preserving vital structures and function. Clinically, HNSCC is divided into three clinical stages: early (~30-40% on presentation), loco-regionally advanced (>50% on presentation), and metastatic or recurrent (~ 10%).
Generally, early-stage disease is treated with single-modality treatments of either surgery or radiation alone. Late-stage disease is best treated by a combination of surgery and radiation, radiation with or without chemotherapy, or all three modalities.
Since the discovery of x-rays, x-ray technology has continued to evolve modern medicine. Today, radiation therapy (RT) is a mainstay in the standard anti-cancer therapeutic tools. Chemotherapy is also an important modality in the management of HNC, improving survival in non-metastatic HNSCC treated with surgery and/or RT with an overall benefit.
Radiosensitization can be done by Chemotherapeutic agents, Targeted Therapy, Hypoxic cells radiosensitizers, and other experimental agents.
Cisplatin is one of the most common CT agents used in combination with RT in HNSCC. Many trials discussed the positive effect of adding Cisplatin to RT on two-year disease free survival, progression free survival, and overall response. Cisplatin has been administered using two schedules in head and neck cancer: intermittent high doses (100 mg/m2 on days 1, 22, and 43) or low weekly doses, (40-50 mg/m2 IV weekly for 6-7wk), but doses and schedules await standardization. Nausea and vomiting and Nephrotoxicity are the most common and dose-limiting side effects of cisplatin.
Gemcitabine is also used in combination with RT in HNSCC. GEM is administered once weekly at dose of 10-50 mg/m2. In general, gemcitabine is a relatively well tolerated drug when used as a single agent. Toxicity is schedule dependent.
Other CT agents include 5-Fluorouracil, Taxanes
A dramatic increase in interest in the use of targeted therapies, specifically targets the epidermal growth factor receptors (EGFR), aiming at improving clinical outcome and minimizing toxicity related to CT agents. Standard dose of Cetuximab is 450mg/m2 on day -7 of RT, then 250 mg/m2 weekly along RT sessions. Other targeted agents (eg. Bortezomib, Intratumoral EGFR Antisense DNA) are still under investigations.
Several strategies to improve tumor oxygenation were developed such as breathing high oxygen content gas under hyperbaric conditions (3 atmosphere) and improving tumor perfusion by nicotinamide, in combination with carbogen breathing. Other strategies to overcome hypoxia induced radioresistance are the use of hypoxic cell radiosensitizers, which mimic oxygen and enhance thereby radiation damage (e.g. the nitroimidazoles) and bioreductive drugs. A meta-analysis of all randomized trials in which some form of hypoxic modification was performed, showed an improved local control and survival, especially in cervix and head-and-neck cancer. Nevertheless, none of the discussed strategies are used in clinical routine because of feasibility and toxicity issues.
Ongoing Experimental studies are investigating the add of new agents, new doses and schedules aiming at improving clinical outcome of CRT.
Finally, standard of care in CCRTH in HNSCC is intermittent high dose platinol, 100mg/m2 on days 1, 22, 43 during RT. For those patients who can't tolerate platinol for renal or cardiac problems, Cetuximab is the approved drug of choice with initial dose 400 mg/m2 1 wk before RT, followed by subsequent doses of 250 mg/m2/week during RT. Unfortunately Cetuximab is still relatively expensive drug.
Head and neck cancer is the fifth most common cancer worldwide, with an estimated annual global incidence of approximately 600,000 cases.
The vast majority of HNC diagnoses (>90%) are of squamous epithelial cell origin and are thus termed head and neck squamous cell carcinomas (HNSCC).
Main risk factors of HNSCC includes smoking, alcohol, chewing tobacco, viral infection, genetic tendency, previous history of head or neck cancer, history of cancer in first-degree family members, exposure to radiation, nutritional disorders, and poor oral hygiene.
HNC treatment is complex and depends on the anatomical location of the tumor and involvement of adjacent organs. The major challenge in treating HNC is obtaining a high cure rate while preserving vital structures and function. Clinically, HNSCC is divided into three clinical stages: early (~30-40% on presentation), loco-regionally advanced (>50% on presentation), and metastatic or recurrent (~ 10%).
Generally, early-stage disease is treated with single-modality treatments of either surgery or radiation alone. Late-stage disease is best treated by a combination of surgery and radiation, radiation with or without chemotherapy, or all three modalities.
Since the discovery of x-rays, x-ray technology has continued to evolve modern medicine. Today, radiation therapy (RT) is a mainstay in the standard anti-cancer therapeutic tools. Chemotherapy is also an important modality in the management of HNC, improving survival in non-metastatic HNSCC treated with surgery and/or RT with an overall benefit.
Radiosensitization can be done by Chemotherapeutic agents, Targeted Therapy, Hypoxic cells radiosensitizers, and other experimental agents.
Cisplatin is one of the most common CT agents used in combination with RT in HNSCC. Many trials discussed the positive effect of adding Cisplatin to RT on two-year disease free survival, progression free survival, and overall response. Cisplatin has been administered using two schedules in head and neck cancer: intermittent high doses (100 mg/m2 on days 1, 22, and 43) or low weekly doses, (40-50 mg/m2 IV weekly for 6-7wk), but doses and schedules await standardization. Nausea and vomiting and Nephrotoxicity are the most common and dose-limiting side effects of cisplatin.
Gemcitabine is also used in combination with RT in HNSCC. GEM is administered once weekly at dose of 10-50 mg/m2. In general, gemcitabine is a relatively well tolerated drug when used as a single agent. Toxicity is schedule dependent.
Other CT agents include 5-Fluorouracil, Taxanes
A dramatic increase in interest in the use of targeted therapies, specifically targets the epidermal growth factor receptors (EGFR), aiming at improving clinical outcome and minimizing toxicity related to CT agents. Standard dose of Cetuximab is 450mg/m2 on day -7 of RT, then 250 mg/m2 weekly along RT sessions. Other targeted agents (eg. Bortezomib, Intratumoral EGFR Antisense DNA) are still under investigations.
Several strategies to improve tumor oxygenation were developed such as breathing high oxygen content gas under hyperbaric conditions (3 atmosphere) and improving tumor perfusion by nicotinamide, in combination with carbogen breathing. Other strategies to overcome hypoxia induced radioresistance are the use of hypoxic cell radiosensitizers, which mimic oxygen and enhance thereby radiation damage (e.g. the nitroimidazoles) and bioreductive drugs. A meta-analysis of all randomized trials in which some form of hypoxic modification was performed, showed an improved local control and survival, especially in cervix and head-and-neck cancer. Nevertheless, none of the discussed strategies are used in clinical routine because of feasibility and toxicity issues.
Ongoing Experimental studies are investigating the add of new agents, new doses and schedules aiming at improving clinical outcome of CRT.
Finally, standard of care in CCRTH in HNSCC is intermittent high dose platinol, 100mg/m2 on days 1, 22, 43 during RT. For those patients who can't tolerate platinol for renal or cardiac problems, Cetuximab is the approved drug of choice with initial dose 400 mg/m2 1 wk before RT, followed by subsequent doses of 250 mg/m2/week during RT. Unfortunately Cetuximab is still relatively expensive drug.
Other data
| Title | Radiosensitizers InSquamous Cell Carcinoma Of Head and Neck | Other Titles | عمرو أحمد السيد علي | Authors | Amr Ahmed Al-Sayed Ali | Issue Date | 2015 |
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