With the development of industrialization, the incidence and mortality rate of lung cancer is now the highest among malignant tumors worldwide and is still on the rise. The two-year survival rate of patients with advanced lung cancer is less than 40%, and patients’ quality of life (QOL) is often very poor. Therefore, there is an urgent need for standardized and comprehensive treatment for lung cancer patients to improve the effectiveness of lung cancer treatment and the quality of life.
The comprehensive treatment strategy for lung cancer is mainly based on the NCCN (The National Comprehensive Cancer Network, NCCN) guidelines. From the perspective of pathological types, lung cancer can be divided into two categories: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Due to the different biological behaviors of the two types of tumors, the treatment modalities are also very different.
I. Comprehensive treatment strategy of NSCLC
(I) General principles of treatment
For resectable NSCLC, surgery is the most important treatment, but even after radical resection, a significant proportion of patients still die from tumor recurrence and/or metastasis. Overall survival (OS); neoadjuvant chemotherapy (preoperative chemotherapy) can play a role in reducing the stage and killing small metastases, providing the possibility of radical surgery for some locally advanced patients; for advanced NSCLC, palliative chemotherapy can improve clinical symptoms, increase QOL and prolong survival. In recent years, targeted therapy for lung cancer has progressed rapidly, and its toxic side effects are significantly lower than those of chemotherapy, which can provide new treatment options for some patients without chemotherapy indications or those who resist chemotherapy, making it possible to benefit from both quality of life and survival time.
(B) The role of chemotherapy in the comprehensive treatment of NSCLC
Chemotherapy, together with surgery and radiotherapy, is known as the three major integrated treatments for malignant tumors. Unlike surgery and radiotherapy, chemotherapy is a systemic treatment by chemical drugs entering the blood circulation, and its therapeutic effect not only targets the local tumor, but also can kill micro metastases or subclinical lesions.
In recent decade, with the introduction of new effective anti-cancer drugs and the increase of new programs, the efficacy of chemotherapy has been significantly improved, and the remission rate (RR) of combined chemotherapy for SCLC has increased to 60%-90%, and CR has reached 30%-40%. CR is 10%~20%.
Chemotherapy can be divided into neoadjuvant chemotherapy (chemotherapy before surgery or radiotherapy), adjuvant chemotherapy (chemotherapy after surgery or radiotherapy) and palliative chemotherapy (also known as palliative chemotherapy) according to the different treatment modalities and purposes.
1. Postoperative adjuvant chemotherapy for NSCLC
Postoperative adjuvant chemotherapy is very important in the comprehensive treatment of NSCLC, and several studies have shown that adjuvant chemotherapy can prolong DFS and OS. adjuvant chemotherapy for stage II and III NSCLC is now recognized to be administered after surgery. adjuvant chemotherapy for stage I NSCLC is still debated. The study showed that 4 cycles of PC (PTX+CBP) chemotherapy after stage IB NSCLC can improve FFS (Failure free survival) and 3-year survival. adjuvant chemotherapy is also recommended for stage IA with high-risk factors (such as poor tumor differentiation, vascular or lymphatic vascular thrombosis, post-wedge resection, and mass near the cut edge).
2. Neo-adjuvant chemotherapy for NSCLC
The significance of neoadjuvant chemotherapy is still controversial, and a meta-analysis in 2008 showed that the main beneficiaries of neoadjuvant chemotherapy were stage II/III patients. In patients with stage IIIa NSCLC in N2, several small clinical studies have demonstrated that neoadjuvant chemotherapy appears to improve the efficacy of chemotherapy + surgery or radiotherapy. It is now more widely accepted that neoadjuvant chemotherapy can improve survival, surgical resection and total resection rates in patients with stage III NSCLC. Neoadjuvant chemotherapy regimen can be implemented with reference to adjuvant chemotherapy regimen.
3. Palliative chemotherapy for NSCLC
Palliative chemotherapy, also known as rescue therapy, is the main treatment for advanced (stage IV) NSCLC. It includes first-line chemotherapy, maintenance therapy, second-line chemotherapy, etc.
(1) Indications for the application of first-line chemotherapy in advanced NSCLC
The first-line standard treatment for metastatic NSCLC is two-drug combination chemotherapy containing platinum. Chemotherapy can prolong survival and improve quality of life, but the benefit is limited to those with good PS (Performance status), so chemotherapy is administered to those with PS score 0-2, while those with PS score 3-4 are treated with Best support care (BSC). The current data show that DDP-based regimens are slightly better than CBP-based regimens, but DDP has a higher GI response and nephrotoxicity than CBP. non-platinum combination regimens are slightly less effective than standard platinum-containing combination regimens, but have less toxic effects and may be an option for those who cannot tolerate or do not want to receive platinum-based chemotherapy.
(2) Maintenance therapy
Maintenance therapy for NSCLC refers to the treatment (including chemotherapy or targeted therapy) that NSCLC patients receive after completing several cycles of standard chemotherapy and having their disease under control. It has been one of the research hotspots in lung cancer academia in recent years.
Some studies have shown that after completing 4 cycles of standard first-line regimens for advanced NSCLC, if the disease is progression-free and the functional score is good, low-toxicity single-agent maintenance chemotherapy or the application of molecularly targeted drugs for maintenance therapy can be chosen to improve survival.
Whether this earlier treatment (so-called early second-line therapy) is beneficial for survival and quality of life improvement still needs more clinical validation.
Maintenance therapy includes prodrug maintenance and conversion maintenance therapy.
Primary maintenance: e.g. biologics in combination chemotherapy can be continued until disease progression or intolerable toxicity; pemetrexed (PEM) chemotherapy is continued after 4-6 cycles of chemotherapy in adenocarcinoma and large cell carcinoma.
Switch to maintenance: first-line cisplatin-containing two-drug combination chemotherapy regimen after 4-6 cycles if no progression switch to pemetrexed (non-squamous) and erlotinib maintenance therapy.
(3) Indications for second-line chemotherapy in advanced NSCLC
Those with disease progression after first-line chemotherapy and PS 0-2 score can be treated with second-line chemotherapy, and the available drugs include TXT, PEM, GEM, PTX, NVB, etc.
(4) Commonly used chemotherapy regimens
a. Commonly used adjuvant chemotherapy regimens
NP regimen: NVB+DDP NVB 25mg/m2, d1,d8; DDP 75mg/m2,d1 q28X4
PC regimen: PTX+CBP PTX 200mg/m2,d1; CBP AUC 6,d1 q21X4
Other available regimens.
GP regimen: GEM+DDP GEM 1250mg/m2,d1,d8; DDP 75mg/m2,d1 q21X4
TP regimen: TXT+DDP TXT 75mg/m2,d1; DDP 75mg/m2,d1 q21X4
b. Commonly used regimens for palliative chemotherapy
First-line regimens: GP, TP, NP, PC regimens are basically the same as adjuvant chemotherapy, with only slight changes in dose, other first-line regimens are
CPT-11/DDP regimen: CPT-11 60mg/m2,d1,8,15; DDP 60mg/m2 q4w
GEM/TXT regimen: GEM 800-1000mg/m2,d1,8; TXT 35-40mg/m2,d1,8 q3w
Second-line regimens.
TXT single agent regimen: TXT 75mg/m2 ,d1 q3w
PEM single-agent regimen: PEM 500mg/m2,d1 q3w
(C) The value of molecular targeted therapy in the treatment of NSCLC
Targeted therapies have been described in detail in the previous chapters, and TKI agents, including Gefitinib and Erlotinib, are widely used in lung cancer treatment.
Gefitinib and Erlotinib are both anilinoquinazoline compounds, which are small molecule tyrosine kinase inhibitors of EGFR. They compete with adenosine triphosphate at the ATP kinase binding site of EGFR, blocking its tyrosine kinase activity and thus blocking the EGFR signaling pathway. For East Asians, women, adenocarcinoma (especially fine broncho-alveolar carcinoma), non-smokers or less smokers.