Gemcitabine in the treatment of non-small cell lung cancer

In Vietnam, the number of new patients as well as the number of patients dying from lung cancer is very high. In 2020, Vietnam has about 26,000 more people with lung cancer, of which a large proportion of patients are locally or regionally advanced and 23 797 deaths from lung cancer.
Lung cancer is usually classified into 2 main types:
Small cell lung cancer (about 10-15%). This type often progresses rapidly, spreading throughout the body, patients often come to the doctor when it is already in the disseminated (late) stage, treated mainly with systemic therapies (chemotherapy, immunotherapy). The group of non-small cell lung cancers (including types such as squamous cell, glandular or large cell type), accounts for about 85%. This type of cancer can be seen when the patient is at an early stage, localized, or at a locally advanced stage - locally, or at a distant metastatic stage.

To diagnose the stage of lung cancer often need to do CT scan (or PET - CT scan), brain MRI, bone scan. In some cases, it is necessary to combine mediastinoscopy, pleural endoscopy, and biopsy of the mediastinum lymph nodes to accurately determine the stage. Other necessary investigations may also be indicated such as: Abdominal ultrasound, abdominal CT scan or full body CT scan, tumor markers...
Note: Most markers Tumor biology is not specific for the diagnosis of lung cancer, so it is not used to definitively diagnose the disease. However, if these substances are elevated without treatment, they can be checked periodically to monitor during treatment.

Treatment of non-small cell lung cancer often has to be based on the stage and ability to apply treatment modalities such as: Surgery - radiation therapy - chemotherapy - immunotherapy, targeted therapy target...
When the disease is at an early stage: Surgery or radiation therapy has the most role. Locally advanced stage: Often, radical surgery is not possible in the first place, it is necessary to combine the above treatment modalities in a harmonious way. Among these highlights the role of chemotherapy, concurrent chemoradiotherapy, and immunotherapy. When the disease is metastatic (stage IV) or the disease recurs after initial treatment, systemic therapy is often required (targeted therapy, immunotherapy, chemotherapy alone or in combination with other therapies). immunotherapy, anti-angiogenesis, etc.). There have been many advances in cancer treatment, thanks to early diagnosis and the discovery of molecular targets for "targeted" treatment. However, a high proportion of lung cancer patients still receive systemic chemotherapy as the primary treatment, as there is no molecular target or marker for targeted therapy or immunotherapy.
For the treatment of lung cancer in such contexts, it is possible to refer to “classic” studies published 10-20 years ago and apply to a few suitable patient groups.
Currently gemcitabine-containing regimens (alone or in combination) are an option in the treatment of lung cancer. The main mechanisms of action of gemcitabine include:
Competition for binding to DNA Complete inhibition of DNA synthesis. When using gemcitabine, note that it should be mixed in 0.9% sodium chloride solution and infused quickly (about 30 minutes). If the infusion time is longer than 60 minutes and is administered weekly, there is an increased risk of bone marrow suppression. The efficacy of gemcitabine in combination regimens has been demonstrated in previously published reputable studies.
Gemcitabine, in combination with cisplatin, is indicated in the first-line treatment of patients with advanced non-small cell lung cancer, adenocarcinoma, and large cell carcinoma. local (stage IIIA or IIIB) or metastatic (stage IV).
For advanced non-small cell lung cancer with advanced squamous cell carcinoma, gemcitabine can be used in first-line therapy (gemcitabine plus cisplatin) and as maintenance therapy (gemcitabine monotherapy) .
In addition, gemcitabine monotherapy may be indicated in elderly patients or in patients with poor physical activity index.

Gemcitabine has been studied previously with a variety of uses in phase I studies of dosing schedules, including daily, twice weekly, biweekly, or according to current use now is every week for 3 weeks, 28 day cycle. Usage in the past can cause flu-like symptoms, low blood pressure, thrombocytopenia, etc. Therefore, nowadays, it is common practice for gemcitabine to be taken every other week for 3 weeks, discontinued. 1 week with a 28 day cycle.
Like other chemotherapeutic drugs, gemcitabine also has some common toxicity related to hematopoietic system such as leukopenia, thrombocytopenia. However, gemcitabine may also experience some side effects not related to hematopoietic system such as nausea, vomiting, skin rash, peripheral edema, nephrotoxicity, proteinuria, microscopic hematuria, hair loss, inflammation oral mucosa,...

REFERENCES
[1] Cardenal F et al. Randomized phase III study of gemcitabin-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 1999 Jan;17(1):12-8.
[2] Sandler AB et al. Phase III trial of gemcitabin plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2000 Jan;18(1):122-30.
[3] Schiller JH et al. Comparison of Four Chemotherapy Regimens for Advanced Non–Small-Cell Lung Cancer. N Engl J Med 2002 Jan 10;346(2):92-8.
[4] Chevalier TL et al. Efficacy of gemcitabin plus platinum chemotherapy compared with other platinum containing regimens in advanced non-small-cell lung cancer: a meta-analysis of survival outcomes. Lung Cancer 2005 Jan;47(1):69-80.
[5] ScagliottiGV et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008 Jul 20;26(21):3543-51.