When 60-year-old Auntie Zhao was diagnosed with lung cancer a month ago, she felt that “the sky was falling”, but with the patience and guidance of her doctors and the comfort and companionship of her children, she slowly recovered and regained her confidence in life.
Choosing the most appropriate chemotherapy regimen
Aunt Zhao had adenocarcinoma of the upper left lung and it was already advanced [clinical stage cT3N3M1a (lung/pleura), stage IVa]. According to our lung cancer guidelines, she needs to undergo genetic testing before treatment, and if she is positive for the driver gene, she can take targeted drugs; if she is negative, chemotherapy is preferred.
Aunt Zhao’s genetic tests were all negative and she could only consider chemotherapy, and her doctor recommended several different options to her:
- PCB regimen (paclitaxel + platinum + bevacizumab),
- AP regimen (pemetrexed + platinum),
- GP regimen (gemcitabine + platinum),
- TC regimen (paclitaxel + platinum),
- DP regimen (docetaxel + platinum),
- NP regimen (vincristine + platinum).
These are all standard first-line chemotherapy regimens for advanced lung cancer, which is better?
In fact, the latter four regimens have been validated in many clinical trials, and the difference in effectiveness and prolonged survival is small: about 30% effective (that’s about 3 out of every 10 patients treated), with a median survival of about 8 months. The AP regimen is more effective in lung adenocarcinoma, with a median survival of 12.6 months and lower toxicity. Bevacizumab has an inhibitory effect on tumor neovascularization. In a large clinical study in China, the PCB regimen was 54% effective and the median progression-free survival of patients was 2.7 months longer than chemotherapy alone. However, bevacizumab is more expensive.
The course of treatment and considerations for the PCB regimen
After a careful comparison, Auntie Zhao chose the PCB regimen: one cycle every 21 days, with dosing on the first day of each cycle and “rest” on days 2-21. It is expected to take 4 to 6 cycles. If it goes well and works, you can consider bevacizumab for maintenance treatment.
Auntie Zhao was very anxious to hear that chemotherapy is very painful and can have many serious adverse effects, such as weakness, easy bleeding and infection due to bone marrow suppression (blood tests reveal a decrease in white blood cells and even a significant decrease in red blood cells, white blood cells and platelets), gastrointestinal reactions such as nausea and vomiting, hair loss, liver and kidney damage, high blood pressure, proteinuria, etc. The doctor reassured her that these adverse reactions are not experienced by everyone and the severity varies from person to person. And because we know what can happen, we can give some “pre-treatment” measures before chemotherapy starts, including anti-vomiting, stomach protection, and prevention of allergic reactions, and we regularly test blood and liver and kidney function indicators to detect the “first signs” early.
After chemotherapy started, as the doctor said, Auntie Zhao did not have the severe nausea and vomiting she had expected, but her appetite was poor for the first 3 to 4 days of chemotherapy.
After the first cycle, she lost a lot of hair; after the second cycle, she simply cut off the rest of her thinning hair and wore a wig, which looked no different from normal hair without looking closely.
After the second cycle, her blood tests showed a significant decrease in “neutrophils” (a type of white blood cell, a “mainstay” of our body’s resistance to infection) and a fever. The doctor considered the possibility of an infection and immediately admitted her to the hospital, where she was isolated in a private room and given antibiotics and drugs to raise her white blood cells, and her temperature gradually dropped to normal and her blood count gradually recovered.
Before the third cycle of treatment, the doctor explained to Auntie Zhao that every two cycles a chest CT would be taken to assess the efficacy of the treatment, and the CT results were very good: the tumor had shrunk by more than 30%, which is known professionally as PR (partial remission). Auntie Zhao was so happy that her doctor lowered the drug dose by 25% on the third chemotherapy session, and all subsequent treatments went well.
After 6 cycles, why did the doctor adjust the regimen?
After 6 cycles of chemotherapy, the doctor recommended a change in the regimen when the chest CT was repeated. Auntie Zhao didn’t understand: “It feels fine, so why change it”? The doctor told her that although her symptoms had not worsened, the disease had progressed on the CT, which indicated that the treatment regimen was not working.
Specifically, there is an internationally accepted standard for evaluating the effectiveness of tumor treatment, called RECIST1.1, according to which if new lesions appear during treatment or if the original target lesion increases by more than 20%, it indicates that the treatment is not working, and the doctor should consider starting a second-line program, which is equivalent to calling a “bench player” after the starter has lost in a soccer game. The doctor should consider starting a second-line program, which is the equivalent of calling in a “bench player” after the starter has lost a football game.
According to our guidelines, this is the time to switch to docetaxel, a drug that can be used to continue chemotherapy.
Summary: Under what circumstances do doctors usually adjust chemotherapy regimens?
In addition to poor efficacy, another reason doctors usually adjust chemotherapy regimens is because of serious adverse reactions, which can be in these situations:
- Vigorous vomiting that affects the body’s electrolyte balance, severe diarrhea more than 5 times a day, bloody diarrhea, or even expulsion of intestinal mucosa.
- If there is myelosuppression, medications may be needed to bring back white blood cells, platelets, and improve anemia. If there is a degree IV myelosuppression (listed below) with fever, be sure to contact your doctor; this condition requires hospitalization and a reduction in the next cycle of chemotherapy drugs.
| Neutrophils ( x10/L) | White Blood Cells ( x10/L) | platelets ( x10/L) | Hemoglobin (g/L) | ||
| 0 | ≥2.0 | ≥4.0 | ≥100 | ≥110 | |
| I degrees | 1.9~1.5 | 3.9~3.0 | 99~75 | 109~95 | |
| II degrees | 1.4~1.0 | 2.9~2.0 | 74~50 | 94~80 | |
| III degrees | 0.9~0.5 | 1.9~1.0 | 49~25 | 79~65 | |
| IV degrees | <0.5 | <1.0 | ＜25 | ＜65 |
- Other serious complications: such as gastrointestinal bleeding or perforation, hemoptysis, pulmonary embolism, etc.
- Toxic reactions in vital organs: such as severe myocardial injury, liver injury, kidney injury, etc.
- Severe allergic reactions.
In summary, physicians will follow guidelines to develop a standardized chemotherapy regimen. In addition, the chemotherapy regimen needs to be “tailored” to the patient in order to achieve the best possible treatment, and the efficacy and adverse effects are closely monitored and adjusted during the course of treatment. This is the balance between “standardization” and “individualization” of treatment in the professional community.
Disclaimer:
Tumor disease and treatment options are extremely complex, and treatment should be fully individualized, and this case does not represent a treatment decision for a “similar patient”. Please seek professional advice from your supervising physician regarding your specific treatment plan.
Co-authors: Dr. Yue-Li Sun Dr. Jiang-Tao Cheng, Guangdong Provincial People’s Hospital, Guangdong Lung Cancer Institute