Lung Cancer Prevention and Screening
● Lung cancer is a unique disease because its main pathogen is an addictive substance manufactured by an industry. Approximately 85%?90% of cases are caused by voluntary or involuntary (secondhand) smoking. Reducing lung cancer mortality requires effective public health policies to prevent smoking from occurring in the first place. The U.S. Food and Drug Administration (FDA) regulates tobacco products, as well as other measures to control tobacco.
● Continued smoking is associated with second primary tumors, treatment complications, drug interactions, other tobacco-related medical conditions, decreased quality of life, and shorter survival.
● Surgeons report results showing that both active smoking and secondhand smoke can cause lung cancer
There is evidence that exposure to secondhand smoke acquired by living with a smoker can increase the risk of lung cancer by 20-30%.
● Everyone should be informed of the health risks, addiction, and deadly threats posed by smoking and secondhand smoke; effective legislation, enforcement, regulation, or other measures to protect all people from tobacco exposure should be planned at the appropriate governmental level (www.who.int/tobacco/framework/final_text/en/).
● The carcinogenic factors of lung cancer also include some highly addictive substances (nicotine), thus compounding the problem. Reduction in lung cancer mortality requires widespread implementation of the Agency for Healthcare Research and Quality guidelines (www.ahrq.gov/path/tobacco.htm#Clinic) for identifying, counseling, and treating patients with nicotine addiction.
● Current or former smokers are at significant risk of lung cancer; chemopreventive agents have not been developed for these patients. If possible, these patients should be encouraged to participate in chemoprevention trials.
● Low-dose CT (LDCT) is recommended to screen for lung cancer in high-risk smokers and former smokers (see the lung cancer screening section of the NCCN guidelines)
Systemic therapy for advanced or metastatic disease
Advanced disease
● The drug regimen that is most likely to be beneficial and has toxicities that are acceptable to both the patient and physician should be the initial treatment for advanced lung cancer.
● Staging, weight loss, physical status (PS), and gender predict survival.
● Platinum-based chemotherapy prolongs survival, improves symptom control, and provides better quality of life than best supportive care.
● The histology of non-small cell lung cancer is important in the choice of systemic therapy.
● For fit patients, newer drug/platinum combinations have shown improvements in overall remission rates (≈ 25%C35%), time to progression (4-6 months), median survival time (8-10 months), 1-year survival (30-40%), and 2-year survival (10%-15%).
● Unsuitable (functional status 3-4) patients of any age do not benefit from cytotoxic drug therapy, but erlotinib may benefit patients with EGFR mutation-positive disease.
First-line therapy
● Bevacizumab + chemotherapy or chemotherapy alone is indicated for patients with advanced or recurrent non-small cell lung cancer with PS 0-1. Bevacizumab should be given until disease progression.
● Erlotinib is recommended as first-line therapy for patients with sensitive EGFR mutations and should not be used as first-line therapy for patients with EGFR-negative mutations or unknown EGFR mutation status.
● Afatinib is indicated for patients with sensitive EGFR mutations.
●Crizotinib is indicated for patients with ALK rearrangement.
● For patients with non-squamous cell carcinoma, cisplatin/pemetrexed has superior efficacy and reduced toxicity compared with cisplatin/gemcitabine.
● For patients with squamous cell carcinoma, cisplatin/gemcitabine has superior efficacy compared with cisplatin/penemetrexed.
● Two-drug regimens are preferred, with a third cytotoxic agent that improves remission rates but does not prolong survival. Monotherapy may be appropriate for some patients.
● Combinations of cisplatin or carboplatin with any of the following agents have been shown to be effective: paclitaxel, docetaxel, gemcitabine, etoposide, vincristine, vincristine, pemetrexed, or albumin-bound paclitaxel.
● If data suggest activity or tolerable toxicity, a new drug/non-platinum combination (e.g., gemcitabine/doxorubicin, gemcitabine/vincristine) is a reasonable choice.
● Remission is evaluated after 1-2 cycles of treatment and every 2-4 cycles.
Maintenance therapy
Continued maintenance therapy refers to the application of at least one agent of first-line therapy for more than 4-6 cycles in the absence of disease progression.
Switching maintenance therapy refers to treatment with an alternative drug that is not a first-line therapy drug after 4-6 cycles of initial therapy in the absence of disease progression.
● Continued maintenance therapy: Bevacizumab combination chemotherapy should be given continuously until disease progression occurs or toxicity is intolerable, as each clinical trial supports this design principle.
Continuation of bevacizumab (class 1) after 4?6 cycles of platinum two-drug chemotherapy in combination with bevacizumab.
For patients other than squamous cell carcinoma, cisplatin and pemetrexed chemotherapy is continued with pemetrexed after 4-6 cycles (Category 1).
For patients other than squamous cell carcinoma, continue treatment with bevacizumab + pemetrexed after 4-6 cycles of bevacizumab, pemetrexed, and cisplatin/carboplatin.
Continuation of gemcitabine therapy (class 2B) after 4-6 cycles of platinum two-drug chemotherapy.
● Conversion to maintenance therapy: Two studies have shown that for patients with progression-free disease after 4-6 cycles of chemotherapy, starting pemetrexed or erlotinib therapy after first-line therapy is beneficial in terms of progression-free survival and overall survival.
For patients other than squamous cell carcinoma, pemetrexed therapy was initiated after 4-6 cycles of first-line platinum-based doublet therapy (Class 2B).
Start erlotinib therapy after 4-6 cycles of first-line platinum doublet chemotherapy (Category 2B).
For patients with squamous cell carcinoma, start docetaxel therapy (Category 2B) after 4-6 cycles of first-line platinum-based doublet therapy.
● Close observation of patients who do not do treatment is a reasonable alternative to maintenance therapy.
Follow-up therapy
● For patients experiencing disease progression, either during or after first-line therapy, single-agent docetaxel, pemetrexed, and erlotinib may be used as second-line therapeutic agents.
Docetaxel is superior to vincristine or isocyclophosphamide.
In adenocarcinoma or large cell carcinoma, pemetrexed is considered to be comparable to docetaxel in efficacy and less toxic.
Remolimumab + docetaxel improves survival compared to docetaxel alone.
Erlotinib is superior to best supportive care.
Afatinib is indicated for the treatment of patients with sensitive EGFR mutations.
Ceritinib is indicated for patients with disease progression or ALK rearrangement who cannot tolerate crizotinib.
Follow-up treatment for disease progression
For patients with EGFR-sensitive mutations or ALK rearrangements who experience objective decline with targeted agents, no other chemotherapeutic agent should be continued after disease progression except for the continued administration of targeted agents (including erlotinib, gefitinib, afatinib, crizotinib, cretinoin ), except under specific circumstances. (See Discussion section)