bubble_chart Overview

Lung cancer originates from the bronchial mucosal epithelium and is also known as bronchogenic carcinoma. Over the past 50 years, many countries have reported a significant increase in the incidence of lung cancer, making it the leading cause of cancer-related deaths among males. The exact cause of lung cancer remains incompletely understood, but extensive data indicate that long-term heavy cigarette smoking is a major contributing factor.

bubble_chart Epidemiology

Most lung cancer patients are male, with a male-to-female ratio of approximately 4-8:1, and the majority of patients are over 40 years old. Those who smoke more than 40 cigarettes a day for many years have a 4-10 times higher incidence of squamous cell carcinoma and undifferentiated carcinoma of the lung compared to non-smokers. The incidence of lung cancer is higher in urban residents than in rural areas, which may be related to air pollution and carcinogens in smoke and dust. Therefore, smoking cessation should be encouraged, and urban environmental sanitation efforts should be strengthened.

bubble_chart Pathological Changes

Lung cancer originates from the bronchial mucosal epithelium, and those confined within the basement membrane are referred to as carcinoma in situ. The cancerous tumor can grow into the bronchial lumen and/or adjacent lung tissue, and can spread through lymphatic, hematogenous, or bronchial routes. The growth rate and metastatic spread of the tumor are related to its histological type, degree of differentiation, and other biological characteristics.

In terms of distribution, lung cancer occurs more frequently in the right lung than in the left, and in the upper lobes than in the lower lobes. Cancerous tumors can develop anywhere from the main bronchi to the small bronchioles. Lung cancer originating from the main bronchi or lobar bronchi, located near the hilum, is called central lung cancer; whereas lung cancer originating from segmental bronchi or below, located in the peripheral parts of the lung, is termed peripheral lung cancer.

bubble_chart Type

Clinically, lung cancer is generally classified into the following four types.

1. Squamous cell carcinoma (also known as squamous carcinoma): This is the most common type of lung cancer, accounting for about 50% of cases. It predominantly affects individuals over the age of 50, with a higher incidence in males. Most cases originate from larger bronchi and are often classified as central lung cancer. Although the degree of differentiation in squamous carcinoma varies, it generally grows and progresses relatively slowly, with a longer disease course. It is more sensitive to radiation and chemotherapy. Lymphatic metastasis occurs first, while hematogenous metastasis occurs later.
2. Undifferentiated carcinoma: The incidence rate is second only to squamous carcinoma, and it is more common in males, with an earlier age of onset. It typically originates from larger bronchi and is classified as central lung cancer. Based on histological cell morphology, it can be further divided into several subtypes, including oat cell, small round cell, and large cell carcinoma, with oat cell being the most common. Undifferentiated carcinoma is highly malignant, grows rapidly, and tends to exhibit early and widespread lymphatic and hematogenous metastasis. Although it is sensitive to radiation and chemotherapy, it has the poorest prognosis among all types of lung cancer.
3. Adenocarcinoma: This type originates from the bronchial mucosal epithelium, with a minority of cases arising from the mucous glands of large bronchi. Its incidence is lower than that of squamous carcinoma and undifferentiated carcinoma. It tends to occur at a younger age and is relatively more common in females. Most adenocarcinomas originate from smaller bronchi and are classified as peripheral lung cancer. Early-stage adenocarcinoma often lacks obvious clinical symptoms and is usually detected during chest X-ray examinations, presenting as round or oval masses. Although it generally grows slowly, hematogenous metastasis can occur early, while lymphatic metastasis occurs later.
4. Alveolar cell carcinoma: This type originates from the bronchial mucosal epithelium and is also known as bronchioloalveolar carcinoma or bronchiolar adenocarcinoma. It is located in the peripheral lung fields. Among all types of lung cancer, it has the lowest incidence and is more common in females. It is generally well-differentiated and grows slowly. Cancer cells grow along the bronchioles, alveolar ducts, and alveolar walls without invading the alveolar septa. Lymphatic and hematogenous metastasis occurs later, but the cancer can spread to other lung lobes via the bronchi or invade the pleura. Alveolar cell carcinoma can be morphologically classified into nodular and diffuse types. The former may present as a single nodule or multiple nodules, while the latter resembles pneumonia in appearance. For localized nodular lesions, surgical resection yields better therapeutic outcomes.

bubble_chart Clinical Manifestations

The clinical manifestations of lung cancer are closely related to the location, size, presence of compression or invasion of adjacent organs, and whether metastasis has occurred. Early-stage lung cancer, especially peripheral lung cancer, often does not produce any symptoms and is mostly detected during chest X-ray examinations. When the tumor grows in larger bronchi, it often causes an irritating cough, typically presenting as paroxysmal dry cough or with only a small amount of white frothy sputum, which is easily mistaken for a common cold. As the tumor continues to grow and affects bronchial drainage, secondary lung infections may occur, leading to purulent sputum with increased volume. Another common symptom is bloody sputum, usually manifesting as blood spots, streaks, or intermittent small amounts of hemoptysis, while massive hemoptysis is rare. Some lung cancer patients may experience symptoms such as chest tightness, wheezing, shortness of breath, fever, and grade I chest pain due to varying degrees of bronchial obstruction caused by the tumor.

In advanced-stage lung cancer, when the tumor compresses or invades adjacent tissues or metastasizes to distant sites, the following symptoms may occur:

1. Compression or invasion of the phrenic nerve, causing paralysis of the ipsilateral diaphragm.
2. Compression or invasion of the recurrent laryngeal nerve, leading to vocal cord paralysis and hoarseness.
3. Compression of the superior vena cava, resulting in venous distension of the face, neck, upper limbs, and upper chest, tissue edema, and elevated venous pressure in the upper limbs.
4. Invasion of the pleura may cause pleural effusion, often bloody. Large amounts of effusion can lead to shortness of breath. Additionally, tumor invasion of the pleura and chest wall may cause persistent and severe chest pain.
5. Tumor invasion into the mediastinum and compression of the esophagus can cause dysphagia.
6. Tumors in the apex of the upper lobe may invade and compress structures at the thoracic inlet, such as the first rib, subclavian artery and vein, brachial plexus, and cervical sympathetic nerves, leading to severe chest pain, venous distension and edema of the upper limbs, arm pain, and motor dysfunction of the upper limbs, as well as ptosis, miosis, enophthalmos, and facial anhidrosis, collectively known as Horner's syndrome.
7. Hematogenous metastasis of lung cancer can produce varying symptoms depending on the affected organ.

Additionally, in rare cases of lung cancer, the tumor may produce endocrine substances, leading to non-metastatic systemic symptoms such as paraneoplastic syndromes (e.g., clubbing, bone arthralgia, periosteal hyperplasia), Cushing's syndrome, myasthenia gravis, gynecomastia in males, and multiple muscular or neural pain. These symptoms may resolve after surgical removal of the lung tumor.

bubble_chart Diagnosis

The diagnostic basis for primary bronchial lung cancer includes: symptoms, signs, x-ray findings, and sputum cytology examination (sputum test). In the diagnostic process, different steps should be taken according to different situations.

(1) X-ray negative, sputum test negative

1. For asymptomatic individuals with three major high-risk factors (male, age ≥45 years, and smoking >400 cigarettes/year), 70–100 mm fluoroscopic x-ray films or chest fluoroscopy and sputum cytology examination should be performed every six months.
2. For those with hemoptysis or/and dry irritating cough accompanied by the three major high-risk factors, repeated sputum cytology examinations should be conducted, along with regular anti-inflammatory treatment; fiberoptic bronchoscopy (fiberoptic bronchoscopy) and television fluoroscopy may be considered. If repeated sputum tests or bronchoscopy remain negative, follow-up examinations should be conducted every two months for one year.

(2) X-ray negative, sputum test positive

1. Exclude upper respiratory tract and esophageal cancer.
2. Perform fiberoptic bronchoscopy, aiming to visualize subsegmental bronchi. If localized mucosal thickening, roughness, or blood traces are observed, brush cytology, lavage, or bronchial wall mucosal puncture should be performed to search for cancer cells. If localized unevenness or significant roughness is found, a biopsy should be considered.
3. Perform television fluoroscopy, changing body positions to focus on detecting small nodular lesions in hidden areas.
4. If no lesion is found after the above examinations, repeat sputum tests, television fluoroscopy, and fiberoptic bronchoscopy every two months. CT scans with fine cuts in suspicious areas may also be performed. Regular follow-ups should continue for at least one year.

(3) X-ray positive, sputum test negative

1. For segmental or lobar pneumonia or obstructive pneumonia suspected to be central lung cancer, fiberoptic bronchoscopy, including transbronchial biopsy (TBB), or selective bronchography should be performed, along with intensified sputum tests.
2. For mass or nodular lesions, localized tomography should be performed. If possible, transbronchial lung biopsy (TBLB), percutaneous lung biopsy, or aspiration cytology should be performed.
3. Conduct at least 12 consecutive sputum tests.
4. If sputum tests remain negative but x-ray strongly suggests lung cancer, exploratory thoracotomy with frozen section biopsy should be performed.

(4) X-ray positive, sputum test positive

1. Prepare actively for surgery.
2. If regional lymph node enlargement is suspected, anteroposterior and lateral oblique tomography can be performed. CT may be performed if necessary. For limited-stage small cell lung cancer, large hospitals should routinely use CT, anteroposterior and lateral oblique tomography, liver ultrasound, bone isotope scanning, and bone marrow aspiration or biopsy smear examination to facilitate treatment planning.

bubble_chart Treatment Measures

1. Selection of Treatment Options for Lung Cancer

2. Surgical Treatment

Among the treatment methods for lung cancer, except for Stage IIIb and IV, surgical treatment or the pursuit of surgical treatment should be the primary approach. Depending on the stage and pathological type, radiotherapy, chemotherapy, and immunotherapy may be added as part of comprehensive treatment. The indications and protocols for small cell lung cancer treatment require continuous refinement through clinical practice.

Regarding the survival period after lung cancer surgery, domestic reports indicate a three-year survival rate of 40–60% and a five-year survival rate of 22.9–44.3%, with a surgical mortality rate below 3%.

(1) Case Selection Generally, the following conditions qualify as candidates for surgical treatment.

1. No distant metastasis (M0), including solid organs such as the liver, brain, adrenal glands, bones, and lymph nodes outside the thoracic cavity.
2. The cancer has not invaded or spread to adjacent thoracic organs or tissues, such as the main pulmonary artery, superior vena cava, esophagus, or cancerous pleural effusion.
3. No paralysis of the recurrent laryngeal nerve or phrenic nerve.
4. No severe impairment of cardiopulmonary function or recent episodes of colicky chest pain.
5. No severe liver or kidney disease or severe diabetes.

Patients with the following conditions should generally be cautious about surgery or require further examination and treatment:

1. Elderly and frail individuals with poor cardiopulmonary function.
2. For small cell lung cancer beyond Stage I, chemotherapy or radiotherapy should be administered first before determining whether surgery is feasible.
3. X-ray findings show suspected metastases in the mediastinum in addition to the primary lesion.

(2) Indications for Thoracotomy Exploration For patients without surgical contraindications and a confirmed diagnosis of lung cancer or high suspicion of lung cancer, the surgical approach can be selected based on specific conditions as outlined in the first section of this chapter. If intraoperative findings reveal that the lesion exceeds the resectable range but the primary tumor is still removable, the primary lesion should be excised. This is referred to as debulking surgery, but in principle, pneumonectomy should be avoided to facilitate postoperative adjuvant therapy.

(3) Naming and Meaning of Surgical Resection for Lung Cancer

1. Palliative Resection (P): Any surgical resection where residual cancer (confirmed by histopathology) remains in the thoracic cavity, or where the resection is considered complete macroscopically (e.g., the bronchial stump appears normal) but microscopic examination reveals residual cancer cells, is termed palliative resection.

Any suspected residual cancerous tissue in the thoracic cavity should be marked with metal clips during surgery to facilitate postoperative radiotherapy.

2. Radical Resection (R): Radical resection refers to the complete removal of the primary cancer and its metastatic lymph nodes.

For lung cancer, radical resection not only requires macroscopic clearance by the surgeon but, more importantly, the complete removal of lymph nodes and the absence of residual cancer cells at the bronchial stump under microscopic examination. To achieve this goal, radical resection for lung cancer is classified into the following four levels.

R1 (Radical 1): Removal of the primary cancer and first-level lymph nodes.

R2 (Radical 2): Removal of the primary cancer and first- and second-level lymph nodes.

R3 (Radical 3): Removal of the primary cancer and first-, second-, and third-level lymph nodes.

R4 (Radical 4): Removal of the primary cancer and first-, second-, third-, and fourth-level lymph nodes.

It should be noted that these four levels of radical resection refer to the extent of lymph node clearance during surgery and do not represent the postoperative outcome.

(IV) Selection of Surgical Procedures for Lung Cancer According to the 1985 International Staging System for Lung Cancer, surgical treatment may be considered for cases in stages 0, I, II, and III, provided there are no contraindications. The principles of surgical resection are as follows: complete removal of the primary lesion and potentially metastatic lymph nodes in the thoracic cavity, while preserving as much normal lung tissue as possible. Pneumonectomy should be performed cautiously.

1. Local Resection: Refers to wedge resection or segmentectomy, which may be considered for very small primary tumors, elderly or frail patients with poor pulmonary function, or cases with well-differentiated, low-grade malignancy.

2. Lobectomy: Suitable for solitary peripheral lung cancer confined to one lobe without significant lymph node enlargement. If the tumor involves two lobes or the intermediate bronchus, bilobectomy (upper and middle lobes or lower and middle lobes) may be performed.

3. Sleeve Lobectomy and Wedge Sleeve Lobectomy: These procedures are often used for right upper or middle lobe lung cancer. If the tumor is located in the lobar bronchus and involves its opening, sleeve lobectomy is indicated; if the opening is not involved, wedge sleeve lobectomy may be performed.

4. Pneumonectomy (generally avoiding right pneumonectomy when possible): Considered cautiously when the lesion is extensive and cannot be removed by the above methods.

5. Carinal Resection and Reconstruction: When the tumor extends beyond the main bronchus to involve the carina or tracheal sidewall (but not exceeding 2 cm): (1) Carinal resection and reconstruction or sleeve pneumonectomy may be performed; (2) If one lobe can still be preserved, efforts should be made to retain it, and the surgical approach can be determined based on the specific circumstances.

Anesthesia Method: Generally, endotracheal intubation under general anesthesia is preferred. For cases with significant bleeding or secretions, double-lumen intubation should be used to ensure airway patency.

(V) Surgical Treatment for Recurrent or Relapsed Lung Cancer

1. Management of Multiple Primary Lung Cancers: For cases diagnosed with multiple primary lung cancers, the treatment principle follows that of the second primary lesion.

2. Management of Recurrent Lung Cancer: Recurrent lung cancer refers to tumor recurrence within the original surgical scar or intrathoracic recurrence related to the primary lesion. The treatment principle depends on the patient's cardiac and pulmonary function and the feasibility of resection.

III. Radiotherapy

(1) Principles of Treatment Radiotherapy is most effective for small cell carcinoma, followed by squamous cell carcinoma, and least effective for adenocarcinoma. However, small cell carcinoma is prone to metastasis, so large-area irregular field irradiation is often used. The irradiation area should include the primary lesion, mediastinum, bilateral supraclavicular regions, and even organs such as the liver and brain, supplemented with drug therapy. Squamous cell carcinoma has moderate sensitivity to radiation, with lesions mainly exhibiting local invasion and relatively slower metastasis, so radical treatment is often employed. Adenocarcinoma has poor sensitivity to radiation and is prone to hematogenous metastasis, making pure radiotherapy less commonly used. In addition to being influenced by pathological type, the sensitivity of tumors to radiation is also affected by factors such as tumor size, degree of tumor cell differentiation, the composition ratio of tumor cell populations, and the condition of the tumor bed. Therefore, before formulating a radiotherapy plan, careful analysis and comprehensive consideration of pros and cons are necessary, and conclusions should not be drawn hastily.

(2) Indications for Radiotherapy Based on the purpose of treatment, it is divided into radical therapy, palliative therapy, preoperative radiotherapy, postoperative radiotherapy, and intracavitary radiotherapy.

1. Radical Therapy: Indications

(1) Early-stage cases with surgical contraindications or refusal of surgery, or cases with lesions limited to 150 cm² (Stage IIIa).

(2) Patients with essentially normal heart, lung, liver, and kidney function, white blood cell count >3×10⁹/L, and hemoglobin >100 g/L.

(3) Karnofsky Performance Status (KPS) ≥60. A detailed treatment plan should be formulated in advance and strictly adhered to without unnecessary changes. Even in the presence of radiation reactions, the goal remains radical tumor eradication.

2. Palliative Therapy: The objectives vary widely, ranging from palliative treatments close to radical therapy (aimed at alleviating suffering, prolonging life, and improving quality of life) to symptom-relief treatments for advanced-stage patients (e.g., pain, paralysis, unconsciousness, dyspnea, and bleeding), which may even serve a comforting role. The number of radiation sessions can range from a few to dozens, depending on the specific circumstances and available equipment, but the principle of not increasing the patient's suffering must be upheld. If significant radiation reactions occur or the KPS score declines during treatment, the regimen may be adjusted as appropriate. Symptom-relief therapy targets the symptomatic area and often employs high-dose, low-fraction irradiation.

3. Preoperative Radiotherapy: Aims to improve surgical resection rates and reduce the risk of intraoperative tumor dissemination. For patients expected to have no difficulty with surgical resection, high-dose, low-fraction preoperative radiotherapy may be used. For large or invasive tumors where resection is anticipated to be difficult, conventional fractionated radiotherapy is preferred. The interval between radiotherapy and surgery should generally be around 50 days, not exceeding three months.

4. Postoperative Radiotherapy: Used for cases where preoperative assessment was insufficient or tumor resection was incomplete. Silver clips should be placed to mark residual lesions for accurate radiotherapy targeting.

5. Intracavitary Brachytherapy: Suitable for localized lesions in large bronchi. Afterloading techniques can be employed, where a catheter is placed at the bronchial lesion via fiberoptic bronchoscopy, and iridium-192 (192Ir) is used for brachytherapy. Combined with external beam irradiation, this can enhance treatment efficacy.

IV. Chemotherapy

Over the past two decades, cancer chemotherapy has advanced rapidly and is widely applied. Current data from domestic and international sources indicate that chemotherapy is relatively effective for small-cell lung cancer (SCLC), whether early or advanced, with even a few reports of radical cure. For non-small-cell lung cancer (NSCLC), it has limited efficacy, primarily palliative, and further improvement is needed. In recent years, the role of chemotherapy in lung cancer has expanded beyond inoperable advanced-stage cases and is now often incorporated as systemic therapy in comprehensive lung cancer treatment.

Table 17-2: Efficacy Rates of Single-Agent Chemotherapy for Different Pathological Types of Lung Cancer Yaodui

0 0

Drug	SCLC (%)	Squamous Cell Carcinoma (%)	Adenocarcinoma (%)	Large Cell Carcinoma (%)
Cyclophosphamide	38	20	20	23
Ifosfamide	63	27	23	36
CCNU	15	30	20	17
ACNU	38	16	17	－
Vincristine	42	10	20
madagascar periwinkle herb alkaloid	24	13	29	20
Etoposide	40	25	12
Doxorubicin	30	20	15	25
Epirubicin	57	7	7	－
Methotrexate	30	25	30	12
Procarbazine	63	27	23	36
Cisplatin	17	19	19	19
Carboplatin	41	7	7	7

(II) Chemotherapy for Small Cell Lung Cancer Due to the biological characteristics of small cell lung cancer, it is currently widely accepted that chemotherapy should be the first choice, except in cases where there is clear evidence of no intrathoracic lymph node metastasis.

1. Indications

(1) Patients with small cell lung cancer confirmed by pathology or cytology.

(2) Patients with a Karnofsky score of 50–60 or above.

(3) Patients with an expected survival time of more than one month.

(4) Patients aged ≤70 years.

2. Contraindications

(1) Elderly and frail patients or those with cachexia.

(2) Patients with severe dysfunction of the heart, liver, or kidneys.

(3) Patients with poor bone marrow function, white blood cell count below 3×10⁹/L, or platelet count below 80×10⁹/L (direct count).

(4) Patients with complications such as fever, bleeding tendency, or infections.

3. Common Regimens: Except in special circumstances, single-drug therapy is generally not used. Internationally and nationally, the following effective regimens are recommended by clinical collaboration groups:

(1) CAO (Shanghai Chest Hospital).

Cyclophosphamide 1000mg/m² Intravenous injection, Day 1

Doxorubicin 50–60mg/m² Intravenous injection, Day 1

Vincristine 1mg/m² Intravenous injection, day 1

Every three weeks constitutes one cycle, and every 2 to 3 weeks constitutes one course of treatment.

(2) COMVP (National Chemotherapy Society Collaborative Protocol)

Cyclophosphamide 500–700mg/m² ² Intravenous injection on days 1 and 8

Vincristine 1mg/m² ² Intravenous injection on days 1 and 8

Methotrexate 7–14mg/m² ² Intravenous or intramuscular injection on days 3, 5, 10, and 12

Etoposide 100mg/m² ² Intravenous drip on days 3–7

Repeat every three weeks, with 2–3 cycles constituting one course of treatment.

3. ECHO (M.D. Anderson Hospital and Tumor Institute)

Etoposide 100mg, intravenous drip (3 hours), on days 3–5

Cyclophosphamide 1000g/m² ² Intravenous drip (1 hour) on day 1

Doxorubicin 60mg/m² ² Intravenous drip (15–30 minutes) on day 1

Vincristine 1mg/m² ² Intravenous drip (15–30 minutes) on days 1 and 8

Every 3 weeks constitutes one cycle, with 3 cycles constituting one course of treatment.

4. CMC (NCI/VA Shanghai Chest Hospital)

Cyclophosphamide 500mg/m² ² Intravenous injection, once weekly ×3 or 1000–1500mg/m² ² Intravenous injection on the second day CCNU 50–70mg/m² ² Oral administration on an empty stomach on the first night

Methotrexate 10mg/m² ² Intravenous push twice weekly ×6 or 30mg/m² ² On the second day

Every three weeks constitutes one cycle, with 2–3 cycles constituting one course of treatment.

5. CV (I.E. Smith, 1987)

Carboplatin 300mg/m² ², intravenous drip on day 1

Etoposide 100mg/m² ², intravenous drip on days 1–3

Every 4 weeks constitutes one cycle, with 4 cycles constituting one course of treatment.

Preoperative and postoperative chemotherapy: For patients who are operable or whose tumors have shrunk sufficiently after chemotherapy to allow surgery, the primary lesion should be removed as much as possible to eliminate the possibility of local recurrence expelling pathogen from exterior. Preoperative chemotherapy generally consists of 2–3 courses to avoid inadequate treatment or excessive fibrosis caused by prolonged treatment, which may complicate surgery. Preoperative chemotherapy is necessary for all patients with confirmed intrathoracic lymph node metastasis. Whether preoperative chemotherapy is needed for stage I patients without intrathoracic lymph node metastasis remains to be explored. Postoperative chemotherapy significantly impacts long-term survival rates and must be emphasized. Generally, 4–6 or more cycles of chemotherapy are recommended. If chemotherapy is effective but the tumor cannot be completely resected during surgery, or if residual lesions are found, localized radiotherapy should also be administered.

(III) Chemotherapy for non-small cell lung cancer: Although there are many effective drugs for non-small cell lung cancer, the response rate is low, and complete remission is rare.

1. Indications:

(1) Pathologically or cytologically confirmed squamous cell carcinoma, adenocarcinoma, or large cell carcinoma that is inoperable (stage III) or has recurred or metastasized postoperatively, or stage I/II patients who are unsuitable for surgery for other reasons.

(2) Surgical exploration or pathological examination reveals the following: ① Residual lesions; ② Intrathoracic lymph node metastasis; ③ Cancer emboli in lymphatics or blood vessels; ④ Poorly differentiated carcinoma.

(3) Patients with pleural or pericardial effusion require localized chemotherapy.

2. Taboo sign: Same as small cell carcinoma

3. Common Regimens: Single-agent therapy has a low efficacy rate for non-small cell lung cancer, so combination chemotherapy should be used. (1) CAP:

Cyclophosphamide 400mg/m² IV, Day 1

Doxorubicin 40–50mg/m² IV, Day 1

Cisplatin 40–80mg/m² IV, Day 1

Repeat every 3 weeks; 2–3 cycles constitute one course of treatment.

Before cisplatin administration, infuse 500ml of 5% glucose solution and 500ml of 5% glucose saline. Then administer cisplatin via IV drip over 1–2 hours. Half an hour later, give 20mg furosemide orally, followed by 500ml Ringer’s solution and 10ml of 10% potassium chloride. To prevent or reduce vomiting, administer 5–10mg dexamethasone via IV drip and metoclopramide intramuscularly or intravenously (total dose 40–90mg).

(2) MFP:

Mitomycin 5–6mg/m² IV drip, Days 1, 15, 29

Fluorouracil 500mg IV drip, Days 10, 12, 17, 19, 31, 33, 38, 40

Cisplatin 30mg IV drip, Days 3–5, 24–26

Repeat every 6 weeks; 2–3 cycles constitute one course of treatment.

(3) CAMB:

Cyclophosphamide 500–700mg/m² IV, Days 1, 8, 15, 22, 29, 36

Doxorubicin 40mg/m² IV drip, Days 1, 22

Methotrexate 7–14mg/m² IV drip, Days 10, 12, 17, 19, 31, 33, 38, 40

Pingyangmycin 10mg IM, Days 3, 5, 11, 13, 17, 19, 24, 26, 31, 33, 38, 40

Repeat every 6 weeks; 2–3 cycles constitute one course of treatment.

(4) PE:

Etoposide 100mg IV, Days 1–5

Cisplatin (DDP) 80mg/m² IV, Day 1 (with hydration), repeat every 4 weeks as one course.

Alternatively, combine with doxorubicin 50mg/m² IV, Day 2.

For intrapleural or intrapericardial injection, aspirate as much fluid as possible before administering the drug. However, to avoid mediastinal shift, limit fluid removal to no more than 1000ml per session. Typically, drain every 5–7 days; if ineffective after 3 sessions, switch drugs. For moderate or larger effusions, perform closed drainage or insert a fine silicone tube for water-seal drainage. After complete drainage, inject the drug, clamp the tube, and remove it after 24–48 hours. Drug options include:

(1) Immunomodulators: Corynebacterium parvum (CP) 7mg dissolved in 40–60ml normal saline. About 80% of patients respond after a single injection.

(2) Chemotherapeutic agents:

① MBP: Mitomycin 5–6mg/m² dissolved in 20–40ml normal saline.

Pingyangmycin: 10–20mg dissolved in 20–40ml normal saline.

Cisplatin: 50–80mg dissolved in 20–40ml normal saline.

② CP:

CTX 500mg/m² dissolved in 20–40ml normal saline.

DDP 50mg/m² dissolved in 20～40ml of normal saline.

The above drugs can be injected into the pleural cavity either in combination or as single agents. When using a single agent, the dose can be increased by one-third. After injection, the patient should be instructed to rest in bed and change positions every 5 to 10 minutes to {|###|}guide the uniform distribution of the medication and ensure full contact with the pleural membrane. For pericardial cavity injections, the dose should be appropriately reduced by one-third, or drugs with milder local reactions should be selected. Commonly used agents include thiotepa (40–60 mg per dose) or DDP (50 mg per dose). Many patients may achieve control of pleural effusion after 1–3 injections, and some therapeutic effect may also be observed for pericardial effusion.

(IV) Precautions for Chemotherapy in Lung Cancer

1. Currently, chemotherapy for lung cancer generally cannot achieve a cure. Therefore, at certain stages of chemotherapy, surgical or radiation therapy should be combined when possible to enhance local or regional tumor control. Meanwhile, during chemotherapy, the highest tolerable dose should be administered based on the patient's condition. For lung cancer chemotherapy, a certain degree of gastrointestinal reactions and bone marrow suppression are unavoidable. The number of treatment cycles should also be appropriately increased based on the patient's response and efficacy, striving to achieve complete remission whenever possible.

2. Intervals between treatment cycles: Due to the prolonged toxicity of existing drugs, which may persist for several weeks after discontinuation, intervals between cycles should be scheduled every 4–6 weeks from the start of chemotherapy. However, the next cycle should only begin after the {|###|}toxic reactions of the guiding medication have subsided.

3. Indications for discontinuing or changing drugs during chemotherapy:

(1) Disease progression after 1–2 treatment cycles, or stabilization followed by deterioration during the rest period.

(2) Toxic reactions reaching grade 3–4, posing a certain threat to the patient's health.

(3) Occurrence of complications, such as fever >38°C or bleeding tendencies.

(4) Rapid deterioration of the patient's general condition, leading to cachexia.

V. Chemotherapy for Complications of Lung Cancer

(I) Chemotherapy for Superior Vena Cava Syndrome For superior vena cava syndrome caused by lung cancer, surgery should be pursued whenever possible, such as superior vena cava repair or replacement. Unfortunately, most patients are already at an advanced stage and lose the opportunity for surgery. If acute superior vena cava obstruction occurs, rapid and effective anticancer drugs should be administered immediately, such as high-dose pulse therapy with cyclophosphamide, nitrogen mustard, or doxorubicin. These drugs can be used alone or in combination, followed by radiotherapy. Note that during the acute phase, radiotherapy should not precede chemotherapy, as radiotherapy may cause tissue {|###|}edema, worsening the superior vena cava obstruction and exacerbating symptoms, even leading to suffocation. For chronic obstruction, radiotherapy is preferred initially. During the acute phase, corticosteroids such as hydrocortisone (100–200 mg intravenously) or prednisone (5–10 mg orally) may be combined with diuretics. Most patients experience relief, but the median survival time is only 2–5 months.

(II) Chemotherapy for Brain Metastases in Lung Cancer The best treatment for brain metastases is localized radiotherapy. However, if no other metastases are present elsewhere in the body and the intracranial lesion is solitary, craniotomy may be performed, followed by chemotherapy and radiotherapy. One patient at our hospital who developed brain metastases after lung cancer surgery underwent resection of the metastatic lesion, followed by chemotherapy and radiotherapy, and has survived for 18 years.

Systemic medication for brain metastases should also be determined based on cell type, but it depends on whether the drug can cross the blood-brain barrier. Lipid-soluble drugs such as carmustine and lomustine can penetrate the blood-brain barrier and are effective against brain metastases. Corticosteroids can alleviate symptoms of cerebral edema, but prolonged use may affect survival time. If the metastasis is unilateral, rapid-acting anticancer drugs can be infused via the internal carotid artery (through the superficial temporal artery or superior thyroid artery).

(3) Chemotherapy for pleural effusion caused by lung cancer At the time of diagnosis, 1% of lung cancer patients have concurrent pleural effusion and no longer qualify for surgical intervention. In such cases, only chemotherapy drugs can achieve temporary efficacy. The commonly used drugs include the following:

1. Nitrogen mustard: Under sterile conditions, aspirate as much pleural effusion as possible (a fine catheter may also be placed). Dilute 0.4 mg/kg with 200 ml of normal saline and inject it into the pleural cavity in a single dose, with a maximum dose not exceeding 20 mg. Immediately after injection, have the patient change positions in multiple directions for about 15 minutes to ensure uniform distribution of the drug over all pleural surfaces. This can be performed once a week. The response rate is 55–87%. Monitor bone marrow function and overall condition before and after each weekly treatment.

2. Atabrine: The response rate is approximately 64–88%. This drug can cause inflammatory adhesions in the pleural cavity, leading to the disappearance of the pleural space. Initially, 50–100 mg can be dissolved in 10 ml of saline and injected into the pleural cavity. If the patient tolerates it well, administer 100–200 mg every 2–5 days until the fluid decreases. Alternatively, a single dose of 600–800 mg may be used. The main side effects include fever, localized pain, and hypotension in some patients.

3. Tetracyclines: Tetracycline is used as a sclerosing agent for the treatment of malignant pleural effusion. Typically, a closed catheter is placed in the pleural cavity, and 500 mg of tetracycline dissolved in 30 ml of normal saline is injected. This is followed by flushing the catheter with 10 ml of saline. The catheter is then clamped for 6 hours while the patient continuously changes positions. Subsequently, the drainage tube is connected to negative pressure suction for about 24 hours and removed once no fluid is detected. Reports indicate that this method successfully controlled fluid accumulation for 3–19 months in patients who did not respond to other drugs (e.g., nitrogen mustard). Kitamura also reported that intrapleural injections of 500 mg of doxycycline 2–3 times over two weeks resulted in complete disappearance of the fluid.

4. Others: Mitomycin is particularly effective for pleural effusion caused by adenocarcinoma, with a single intrapleural dose of 6–12 mg. Additionally, nitrocaphane (30–40 mg per dose) and 5-fluorouracil (750–1000 mg per dose) can be used. Other options include colloidal gold (198Au), colloidal phosphorus (32P), and vaccines such as poliomyelitis vaccine or types II and III smallpox vaccine.