Radiotherapy has been the standard of care for nasopharyngeal carcinoma and is a treatment of choice for patients without distant metastases. A large sample of studies on the efficacy of conventional radiotherapy for nasopharyngeal carcinoma with combined facial and cervical fields as the main fields reported that the 5-year local and regional control rates were about 81.7%-85%, and the 5-year overall survival rates were 59%-75%, with local recurrence and distant metastases as the main reasons for failure [1-4]. Distant metastasis has become the main cause of failure.
The rate of lymph node metastasis in nasopharyngeal carcinoma is high, with about 40% to 50% of patients complaining of neck lumps at the time of initial diagnosis, and more than 70% of patients found to have metastasis in the lymph nodes of the neck during examination. The rate of bloodborne distant metastasis of nasopharyngeal carcinoma is high, accounting for about 10%-13% of patients initially treated, and the rate of distant metastasis among deceased patients is as high as about 45%-60% [5], thus the rate of early patients at clinical diagnosis is low, therefore, comprehensive treatment of nasopharyngeal carcinoma is essential. It has been shown that the use of chemotherapy combined with radiotherapy in the treatment of mid- to late-stage nasopharyngeal carcinoma can improve the local control rate and reduce the distant metastasis rate, thus improving the overall survival rate and tumor-free survival rate. Currently, clinical studies on neoadjuvant chemotherapy p concurrent chemotherapy p adjuvant chemotherapy p palliative chemotherapy p chemotherapy sensitization and the combination of the above-mentioned chemotherapy modalities have been widely carried out at home and abroad.
I. Neoadjuvant chemotherapy
Neoadjuvant chemotherapy refers to chemotherapy used before radiotherapy, also known as induction chemotherapy. Its mechanism of action is to kill potential micro-metastases and thus reduce the risk of distant metastases; to reduce the load of nasopharyngeal primary tumor and metastatic lymph nodes in the neck before radiotherapy, which is more conducive to the design of radiotherapy plan and thus improve the local and regional control rate. Neoadjuvant chemotherapy has the following advantages: the general condition of the patient before radiotherapy is good and has better tolerance to chemotherapy; there is no fibrosis caused by radiotherapy and the tumor blood supply is good, which is conducive to the distribution and action of chemotherapy drugs. However, because chemotherapy is done first and local radiotherapy is delayed, the effect of radiotherapy sensitization is weaker and the inhibitory effect on radiotherapy-resistant tumor cells is smaller, in addition, chemotherapy can accelerate the re-proliferation rate of tumor cells.
In 1989, the International Nasopharynx Cancer Study Group and the Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group organized a large multicenter prospective clinical study to examine the value of neoadjuvant chemotherapy almost simultaneously. The former study included centers from Algeria, Croatia, Greece, France, Malaysia, Morocco, Portugal, Saudi Arabia, Spain, and Turkey, and used neoadjuvant chemotherapy regimens of Bleomycin, Epirubicin, and BLM+ EPI + DDP for 3 courses; a total of 339 patients with N-stage ≥2 (1987 UICC stage) were enrolled in the study, of which 339 were in the neoadjuvant group (chemotherapy regimen of Bleomycin + EPI + DDP). The median follow-up time was 49 months; compared with radiotherapy alone, neoadjuvant chemotherapy significantly reduced the incidence of local recurrence and distant metastases and improved disease-free survival, but failed to improve overall survival, while treatment-related toxicity resulted in an 8% mortality rate[6] . In the latter study, six treatment centers in Southeast Asia were enrolled with two to three courses of chemotherapy with Epirubicin and DDP; 334 cases were enrolled (Ho’s stage III, IV or N ≥ 3 cm), of which 167 were in the neoadjuvant chemotherapy group and 167 in the radiotherapy-only group; the median follow-up time was 30 months; neoadjuvant chemotherapy failed to improve recurrence-free survival compared with radiotherapy-only. However, among the 286 patients (134 in neoadjuvant chemotherapy and 152 in radiotherapy alone) who had completed all treatments and could be evaluated for treatment response, there was a trend of increasing the recurrence-free survival rate, P=0.053, while the differences in distant metastasis rate and overall survival rate were not statistically significant; further analysis of patients with N > 6 cm showed that neoadjuvant chemotherapy improved the recurrence-free survival rate but failed to reduce the distant metastasis rate and overall survival. Further analysis of patients with N > 6 cm showed that neoadjuvant chemotherapy improved recurrence-free survival but failed to reduce distant metastasis rate, and overall survival tended to improve [7]. Chua et al [8] further analyzed the long-term outcome of 183 patients enrolled in the Asia-Pacific Nasopharyngeal Carcinoma Study Group in Hong Kong, with a median follow-up of 70 months, and no statistically significant differences in recurrence-free survival, distant metastasis-free survival, and overall survival between the neoadjuvant chemotherapy and radiotherapy alone groups. The neoadjuvant chemotherapy regimen was DDP + 5-FU + BLM for 2 courses, resulting in 219 cases enrolled in neoadjuvant chemotherapy and 221 cases enrolled in radiotherapy alone; 85% of the cases were followed up for more than 5 years, and the neoadjuvant chemotherapy and radiotherapy groups did not show any statistical difference in local recurrence-free survival, tumor-free survival, distant metastasis-free survival and overall survival, but the neoadjuvant chemotherapy group showed no statistical difference in T3 survival, tumor-free survival and overall survival. local recurrence-free survival was significantly higher in the neoadjuvant chemotherapy group in patients with T3 , T4 stage [9].
From the results of the above prospective clinical randomized studies combined with the results of some retrospective studies of larger cases[10] , most studies showed that neoadjuvant chemotherapy improved local regional control rates in patients with T advanced and N advanced stages, and some results showed a reduction in distant metastasis rates, but in terms of long-term outcomes, the majority of studies did not show an overall survival benefit.
II. Synchronized chemoradiotherapy
Synchronized chemoradiotherapy refers to the use of chemotherapy in conjunction with radiation therapy. It works by direct killing of tumor cells by chemotherapeutic drugs; or synchronizing the tumor cell cycle and arresting it in the G2/M phase; or increasing the tumor-killing effect of radiotherapy by inhibiting the repair of sublethal damage to tumor cells. The advantage of synchronized chemoradiotherapy over other modalities of combined chemoradiotherapy is that there is synergy with radiotherapy, the tumor blood supply is not destroyed, there is no neoadjuvant chemotherapy followed by tumor in accelerated proliferation rate, and there is no delay in the appearance of radiotherapy. Its main goal is not only to improve local control, but also to reduce the occurrence of distant metastases, as has been demonstrated in other head and neck tumors. Many studies have suggested that local area failure (especially lymph node recurrence) is positively correlated with the occurrence of distant metastases, so the mechanism of simultaneous radiotherapy to reduce distant metastases may be: killing of micro-metastases by chemotherapeutic drugs and reducing the rate of distant metastases by increasing the rate of local area control. The chemotherapy regimen for the concurrent radiotherapy group was a lower dose PF regimen (DDP 20 mg/m2 , 5-FU 400 mg/m2 , 96 h continuous infusion) at weeks 1 and 5 of radiotherapy; the median follow-up time for the whole group was 65 months, and the 5-year progression-free survival and overall survival rates were significantly higher in the concurrent radiotherapy group than in the radiotherapy-only group (71.6% vs. 53.0%, P = 0.0012 and 72.3%, respectively). Chan et al[12] analyzed the results of a prospective study in Hong Kong and further showed that concurrent radiotherapy significantly improved the progression-free survival and overall survival of patients with T3-4. and overall survival.
Langendijk et al [13] and Baujat et al [14] reported in 2004 and 2006, respectively, 2 meta-analyses based on literature data and independent databases summarizing randomized p double-blind and setting-controlled clinical trials since 1975 to analyze the effect of chemotherapy on radiotherapy efficacy in locally advanced nasopharyngeal carcinoma. Chemotherapy resulted in a 6% absolute benefit in 5-year overall survival and a 10% benefit in disease-free survival for locally advanced nasopharyngeal carcinoma treated with radiotherapy, with the benefit mainly coming from the concurrent chemoradiotherapy group; neoadjuvant and adjuvant chemotherapy did not significantly improve overall survival.
For concurrent chemoradiotherapy, the optimal chemotherapeutic agent and regimen are still debated. Currently, the following regimens are often used: single drug administered in small doses daily; single drug administered weekly or single drug/combination administered once every 3 weeks.
Third, adjuvant chemotherapy
Adjuvant chemotherapy is chemotherapy administered after radiation therapy. Rossi et al[15] reported the results of a prospective clinical study conducted in Milan, Italy, in which 229 patients with stage II-IV (Ho’s staging) were randomly divided into radiotherapy + adjuvant chemotherapy group (113 patients) and radiotherapy alone group. In the adjuvant chemotherapy group, 6 courses of VCA (VCR, CTX and ADM) were used after radiotherapy; 13 patients in the adjuvant chemotherapy group did not receive adjuvant chemotherapy after enrollment, 24 patients received more than 6 courses of chemotherapy, and 6 patients did not complete 6 courses of chemotherapy due to severe acute toxicity reactions; after 4 years of follow-up, the differences in disease-free survival and overall survival rates between the adjuvant chemotherapy group and the radiotherapy-only group were not statistically significant. In Taiwan, Chi et al [16] randomized 157 stage IV (M0) patients into adjuvant chemotherapy and radiotherapy-only groups with 24-h infusion of DDP (20 mg/m2 ), 5-FU (2,200 mg/m2 ), and tetrahydrofolate (120 mg/m2 ), followed by radiotherapy once a week for a total of 9 times, with a median follow-up of 49.5 months, and analyzed 154 patients (77 each in the adjuvant and radiotherapy-only groups) available for evaluation. The 5-year local recurrence-free survival (54.4% vs. 49.4%), local recurrence-free survival (49.4% vs. 51.3%), distant metastasis-free survival (59.6% vs. 58.4%), and overall survival (54.4% vs. 60.5%) were not statistically significant between the two groups; the incidence of moderate and severe acute toxic reactions was significantly higher in the adjuvant chemotherapy group than in the radiotherapy-only group, and 6 patients experienced fatal acute toxic reactions. Due to the destruction of blood flow and lymphatic circulation after radiotherapy, the local drug concentration decreased during adjuvant chemotherapy; meanwhile, the acute toxic reactions increased significantly, and the nutritional status and psychological quality of patients after radiotherapy were poor, which made it difficult to adhere to the completion of adjuvant chemotherapy; in addition, the results of existing prospective clinical studies all showed that adjuvant chemotherapy had no significant therapeutic gain. Therefore, adjuvant chemotherapy is basically not used to treat locally advanced patients, but is mostly used as a follow-up measure to further control distant metastases on the basis of other combined chemoradiation modalities.
IV. Combined application of simultaneous and adjuvant chemotherapy
Considering the low dose of chemotherapy in concurrent radiotherapy and the uncertain effect on distant metastasis, while the main purpose of adjuvant chemotherapy is to reduce the occurrence of distant metastasis, many investigators have combined the two for the treatment of patients with advanced nasopharyngeal carcinoma. Currently, there are four main prospective analyses of simultaneous radiotherapy + adjuvant chemotherapy [17,18,19,20]. The major breakthrough in the combined radiotherapy treatment of locally advanced nasopharyngeal carcinoma first originated from the report of AL-sarraf et al [16] on study 0099, a prospective clinical study initiated by the Southwest Oncology Group (SWOG) in the United States with the participation of the Radiation Therapy Oncology Group (RTOG) and the Eastern Collaborative Oncology Group (ECOG), using a randomized controlled approach, in which patients with stages III and IV (1987 AJCC/ UICC The chemotherapy regimen for the chemotherapy group was DDP 100 mg/m2 administered intravenously on days 1, 22 and 43 during radiotherapy, followed by DDP 80 mg/m2 d1 and 5-FU 1,000 mg/ (m2.d) d1 to d4 after radiotherapy, repeated every 4 weeks, for a total of 3 courses. The total number of cases enrolled in the study was 193, of which 147 cases (78 cases in the chemotherapy group and 69 cases in the single radiation group) were available for analysis. The 3-year progression-free survival rates were 69% and 24% in the chemotherapy and monoradiotherapy groups, respectively, with P < 0.001; the 3-year overall survival rates were 78% and 47%, respectively, with P < 0.005. Hoffman et al [21] showed that from 1989 to 1997 (before the publication of the report by AL-sarraf et al [16]), only 38.2% of stage III and IV patients were treated with concurrent adjuvant chemotherapy, whereas from 1998 to 2001 (before the publication of the report by AL-sarraf et al [16]), only 38.2% of the total cases were treated with concurrent adjuvant chemotherapy. In the years 1998-2001 (after the publication of AL-sarraf et al [16]), the use of concurrent and adjuvant chemotherapy reached 65.1%. This shows that the combination of concurrent and adjuvant chemotherapy has gradually become the standard of care for locally advanced nasopharyngeal carcinoma in the United States. However, this study is controversial in Asian countries and Hong Kong because of the short progression-free survival time (mean 13 months) and low 3-year progression-free survival rate in the radiotherapy-only group in this study. In contrast, a study by Chan et al [22] in Hong Kong reported a 72% disease-free survival rate in the radiotherapy-only group and a 2-year survival rate of 80.5%, which is similar to the disease-free survival rate in the US study with adjuvant chemotherapy during the same period. Is it because of the higher dose intensity of radiation therapy used by radiation therapists in Hong Kong? Or did the difference in histologic type between US and Asian patients affect the efficacy of radiation therapy (40.8% of patients with WHO type 3 in this study, compared with more than 90% of patients with WHO type 3 in southern China and Hong Kong and Southeast Asia)? Or is it that too many patients in this group (26.7%) did not complete the treatment as planned due to toxic effects of chemotherapy that led to the bias of the results? In September 1997, Wee et al [18] designed a similar prospective study in Singapore, enrolling 221 patients, 45% and 54% in stage III and IV (1997 AJCC/UICC stage), respectively, all with WHO type 2 and 3 histology; the concurrent chemotherapy regimen was DDP 25 mg/m2, d1 to d4, at weeks 1, 4, and 7 of radiotherapy; adjuvant chemotherapy was DDP 20 mg/m2, d1 to d4, and 5-FU 1,000 mg/m2, d1 to d4, at weeks 11, 15, and 19. The results showed that 5 cases in the radiotherapy-only group failed to complete radiotherapy as planned for various reasons, and 83 cases (74%) in the chemotherapy group did not complete all chemotherapy (29% of them did not complete the same period, 31% of patients did not receive adjuvant chemotherapy, and 35% reduced the dose and course of adjuvant chemotherapy or replaced it with other drugs); median follow-up was 3.2 years, and the cumulative distant metastasis rate was reduced in the chemotherapy group compared with the radiotherapy-only group. The 2-year cumulative distant metastasis rate was reduced by 13% , P = 0.002 9 , and the 3-year disease-free survival rate was increased by 19% , P = 0.009 3 , and the 3-year overall survival rate was increased by 15% , P = 0.006 1 . Although the authors concluded that their study confirmed the results of the 0099 study, the number of cases that did not complete treatment as planned was higher in the chemotherapy arm of the study. To further validate the clinical results of the chemotherapy regimen in the 0099 study in an Asian population, a multicenter prospective clinical study of concurrent plus adjuvant chemotherapy was organized in Hong Kong in 1999 with six hospitals in Hong Kong and one hospital in Toronto, Canada. The concurrent radiotherapy regimen was the same as in the 0099 study, and Lee et al [19] reported their findings: from 1999 to 2004, a total of 348 patients were enrolled, with 2 cases in each of the two groups not treated according to the treatment protocol plan; 65% of the concurrent radiotherapy group completed all 6 courses of chemotherapy, and 79% had ≥5 courses of chemotherapy; the incidence of grade 4 acute toxic reactions was significantly higher in the concurrent radiotherapy group than in the The median follow-up time was 2.3 years; the 3-year failure-free survival rate was significantly higher in the concurrent radiotherapy group than in the radiotherapy alone group (72% vs. 62%, P = 0.027), and the local failure-free survival rate was significantly higher than in the radiotherapy alone group (92% vs. 82%, P = 0.005), while the metastasis-free survival rate and overall survival rate were not statistically different between the two groups (76% vs. 73%, P = 0.005). Cox regression analysis by Kwong et al [20] showed that synchronized chemoradiotherapy was an independent factor in overall survival. In contrast, adjuvant chemotherapy had no significant effect on either tumor control rate or survival, and the effect of synchronous chemoradiotherapy + adjuvant chemotherapy group on survival was mainly the effect of synchronous chemotherapy. It should be noted that radiotherapy with chemotherapy for nasopharyngeal cancer has different degrees of benefit in different clinical cases, but it is also prone to chemotherapy toxicities and complications. Chan et al [12] reported a significant increase in grade 3-4 adverse effects in the synchronous radiotherapy group, with a 13% increase in the incidence of acute mucositis, a 12% increase in gastrointestinal reactions, a 14.8% increase in the incidence of hematologic toxicity, and a 23.6% increase in the rate of weight loss exceeding 10%. Wee et al [18] reported a 75% incidence of 3rd degree mucositis in concurrent radiotherapy, 40% of patients required lower doses of chemotherapy, and 58% of patients failed to complete adjuvant chemotherapy as required. In the VUMCA I study (a phase III clinical study), a treatment-related mortality rate of 8% was reported [6]. Therefore, chemotherapy combined with radiotherapy can improve the efficacy of advanced NPC, but it also significantly increases the toxic side effects of treatment, which should be given sufficient attention in clinical work. Thus, how to continue to find new highly efficient and low-toxic antitumor drugs is still an urgent problem to be solved in the future.
V. Palliative chemotherapy
For patients with distant metastases, chemotherapy as a systemic treatment is of great significance. Many literature reports that a few patients with distant metastases can obtain long-term survival through chemotherapy. Patients who have relapsed after radiotherapy can also be considered for chemotherapy due to the limitations of many factors, such as the short interval between the relapse and the first course of radiotherapy and the serious sequelae caused by radiotherapy.
The use of platinum-based drugs has been a landmark in palliative chemotherapy. Response rates of 28% and 22% for cisplatin and carboplatin monotherapy, respectively, have been reported in the literature [23]. Studies in the 1980s showed that cisplatin-based combination chemotherapy improved response rates even further (~50-90% and CR ~5-30%) compared to single-agent and non-platinum-based combination chemotherapy. Cisplatin + 5-Fu gradually became a standard first-line chemotherapy regimen (cisplatin, 100 mg/ m2; 5-Fu,1000 mg/ m2, 3-5 days of infusion) with reported response rates of 66-78% and a median survival time of 11 months [24,25]. In the 1990s, some studies attempted 3 or more drugs in multidrug combinations to optimize chemotherapy response. Although a large increase in response rates was reported in some phase II clinical trials, there was a corresponding increase in toxic effects and concomitant cases of infectious death. A study from Europe reported a durable response rate of 80% (20% CR) with a three-drug combination of DDP + Bleomycin + 5-Fu [26]. However, a study from Asia did not achieve the above efficacy; instead, grade 3-4 neutrophil decline occurred in 36% of cases, accompanied by three infectious deaths [27]. Other studies have used 4-5-drug combination chemotherapy and reported response rates of 52-86%, with a dramatic increase in the incidence of grade 3-4 neutropenia to greater than 80% and an increase in treatment-related mortality to 9%. Although multi-drug combination chemotherapy improved response rate, it did not improve the corresponding survival rate, and the toxic reactions increased, so it was not consistent with the principle of palliative care.
VI. Common chemotherapy regimens and considerations for advanced nasopharyngeal carcinoma
(a) Concurrent ± adjuvant chemotherapy regimens (representative randomized p double-blind and controlled group phase III clinical trial protocols in the literature)
⒈ (administered concurrently with radiotherapy), cisplatin (DDP) 100 mg/m2, intravenously, day 1, day 22, day 43.
(administered after radiotherapy), DDP 80mg/m2,intravenous, day 1.
5-Fu 1,000mg/m2, continuous intravenous infusion, days 1 to 4.
DDP + 5-Fu regimen 1 cycle every 21 days for 4 cycles.
Precautions.
(1) Concurrent radiotherapy and adjuvant chemotherapy may aggravate oral mucositis and difficulty in eating and swallowing; pay attention to enhance symptomatic management and nutritional support therapy.
(2) The main toxic side effects are bone marrow suppression p nausea p vomiting p skin mucosal reactions, etc. Nausea p vomiting is mainly caused by cisplatin and antiemetic drugs should be used.
(3) Cisplatin hydration.
(4) Fluorouracil can develop hand-foot syndrome, which should be reduced or discontinued. Cox-2 inhibitor celecoxib has been reported to prevent the occurrence of hand-foot syndrome.
(PAK) (administered concurrently with radiotherapy), cisplatin (DDP) 25 mg/m2, intravenously, days 1 to 4; days 22 to 25; days 43 to 46.
(administered at the end of radiotherapy), DDP 80mg/m2, intravenous, day 1.
5-Fu 1,000mg/m2, intravenous drip, days 1 to 4.
DDP + 5-Fu regimen 1 cycle every 21 days for 4 cycles.
Precautions: as above.
DDP 40 mg/m2, intravenous drip, once weekly for 8 weeks (concurrent with radiotherapy).
Precautions.
(1) Concurrent radiotherapy may aggravate oral mucositis and difficulty in eating and swallowing; pay attention to strengthen symptomatic management and nutritional support therapy.
(2) The main toxic side effects are bone marrow suppression p nausea p vomiting p skin mucosal reactions, etc. Nausea p vomiting is mainly caused by cisplatin and antiemetic drugs should be used.
(3) Hydration of cisplatin.
⒋ (concurrent with radiotherapy), DDP 20mg/m2, intravenous drip, days 1 to 4, days 22 to 25.
5-Fu 400 mg/m2, continuous intravenous infusion, days 1 to 4, days 22 to 25.
DDP + 5-FU regimen 1 cycle every 21 days for 2 cycles.
Caution: Same as above for cisplatin + fluorouracil regimen.
Be careful (concurrent with radiation therapy) with paclitaxel (PTX) 50 mg/m2, IV drip, once weekly for 7 weeks.
Precautions.
(1) Concurrent radiotherapy may aggravate oral mucositis and difficulty in eating and swallowing; pay attention to enhance symptomatic management and nutritional support therapy.
(2) The main toxic side effects are allergic reactions p granulocytopenia p paclitaxel can cause joint muscle aches and pains.
(3) Dexamethasone can be taken orally or injected quietly 6-12 hours before the intravenous paclitaxel drip (for details of the dose, please refer to the instructions of each manufacturer), and Benadryl 50mg can be injected intramuscularly half an hour before, which is aimed at preventing the allergic reaction of paclitaxel.
(4) Prophylactic dexamethasone is required and should be used with caution in patients with diabetes mellitus. Paclitaxel should be avoided in patients with uncontrolled diabetes mellitus.
(ii) neoadjuvant chemotherapy regimen (representative randomized p double-blind and controlled phase III clinical trial protocol in the literature)
⒈ DDP 60 mg/m2, intravenous, day 1.
Epirubicin (EPI) 110 mg/m2, intravenous push, day 1.
Repeat every 3 to 4 weeks for 2 to 3 cycles.
Precautions.
(1) The main toxic side effects are bone marrow suppression p nausea p vomiting p skin mucosal reactions, etc. Nausea p vomiting is mainly caused by cisplatin and antiemetic drugs should be used.
(2) Cisplatin hydration.
(3) Cumulative dose of epirubicin should not exceed 900mg/m2.
Pepto DDP 80mg/m2,IV drip, day 1.
5-Fu 800mg/m2, continuous intravenous infusion, days 1 to 4.
Repeat every 3 weeks for 2 cycles.
Precautions: same as above cisplatin + fluorouracil regimen.
DDP 100mg/m2,intravenous infusion, day 1.
5-Fu 800mg/m2, continuous intravenous infusion, days 1 to 5.
Bleomycin 10mg/m2,intravenous or intramuscular, day 1 and day 5.
Repeat every 3 to 4 weeks for a total of 2 to 3 cycles.
Precautions.
(1) Same as above for cisplatin + fluorouracil regimen.
(2) Bleomycin should be given intravenously slowly over no less than 10 minutes. Post-injection febrile reactions are common, and death due to anaphylaxis is occasionally seen. It can cause skin pigmentation. Long-term administration may cause pulmonary fibrosis, the cumulative dose should not exceed 400mg, otherwise the incidence of dose-related pulmonary fibrosis is extremely high.
(C) the palliative chemotherapy program
⒈ cisplatin 80-100mg/m2,intravenous drip, day 1.
or 30 mg/m2,intravenous drip, days 1 to 3.
Fluorouracil 1,000mg/m2, continuous intravenous drip, days 1 to 4.
Once every 3 weeks for 4 to 6 cycles as appropriate.
Caution: Same as above cisplatin + fluorouracil regimen.
PAPER Paclitaxel 135 mg/m2, intravenous drip over 3 hours, day 1.
OR
Doxorubicin 100mg/m2, IV drip over 1 hour, day 1.
cisplatin 75mg/m2, IV drip, day 1.
Once every 3 weeks, consider 4 to 6 cycles as appropriate.
Precautions.
(1) The main toxic side effects are allergic reaction p granulocytopenia p nausea p vomiting, nausea p vomiting mainly caused by cisplatin, antiemetic should be used, paclitaxel can cause joint muscle pain, doxorubicin can have body fluid retention.
(2) Cisplatin hydration.
(3) Dexamethasone can be taken orally or injected quietly 6-12 hours before the intravenous paclitaxel drip (for details of the dose, please refer to the instructions of each manufacturer), and Benadryl 50mg can be injected intramuscularly half an hour before, which aims to prevent the allergic reaction of paclitaxel.
(4) Dexamethasone 7.5 mg orally twice daily for 3 days prior to doxorubicin administration to prevent fluid retention. A healthcare professional must be present within 15 minutes after the start of the drip to closely observe blood pressure p respiration p pulse and the occurrence of allergic reactions.
(5) Prophylactic use of dexamethasone is required; therefore, it should be used with caution in patients with diabetes mellitus. Paclitaxel should be avoided in patients with uncontrolled diabetes mellitus.