口腔药物学：口腔临床药物使用实例分析与讨论

1、Case Study,#1：Infection of OMF region #2：Chemotherapy for SCC of FOM (T4N2M0) #3：Perioperative use of antibiotics for patients with TSCC (T3N1Mx) #4：Perioperative use of antibiotics for patients with ORN #5：Analgesic therapy for patients with advanced oral cancer,Representative Cases,* Blue, teachin

2、g; Black, self-study,Case #1,XXX, male, 18,- Infection of OMF region,How to do?,Case #1,Step 1 - History,- Infection of OMF region,How to ask about the history？,Case #1,Step 1 - History,- Infection of OMF region,Main complains Site Time Duration Progression Accompanied symptoms Treatment and effects

3、 ,Case #1,XXX, male, 10 Retromolar swelling and pain for 5 days Reddening and swelling of OMF region for 3 days Fever for 2 days? anymore? next?,- Infection of OMF region,Case #1,Step 1 - History,- Infection of OMF region,Local - reddening swelling thermalgia function disorder,Systemic - high fever

4、chill dehydration hyperleukocytosis general malaise,Case #1,Step 2 - physical examination,- Infection of OMF region,Local - reddening swelling thermalgia function disorder,Systemic - vital signs, anymore?,Case #1,Step 3 - laboratory examination,- Infection of OMF region,blood test WBC neutrophilic g

5、ranulocyte,- imaging examination ultrasonic，CT，MRI,Blood test results,Puncture bacterial culture drug sensitive test,Laboratory test,Case #1,Step 4 - treatment,- Infection of OMF region,Indications for antibiotic therapy ?,Antibiotic therapy,An infection is genuinely present The infection is respond

6、 to antibiotic Severe infection Prevent serious infection,Indications,Case #1,Step 4 - treatment,- Infection of OMF region,Indications for antibiotic therapy ?,How to control the infection ?,Treatment plan 1 Penicillin Na 9.6 106 U ivgtt. qd 30,How to control the infection ?,Treatment plan 2 cefepim

7、e (头孢吡肟) 2.0 ivgtt. qd 3,Wait or antibiotic treat first ? What are the general principles ?,Principle,According to the indications Fever of unknown reasons According to the characteristics of bacterium According to the patients condition Avoid local application in skin and mucous membrane Strictly c

8、ontrol prophylactic use of antibiotics Combination use according to the indications,Empiric therapy,Predictable organisms Penicillin is the first choice Clindamycinpenicillin-allergic patients For compromised hosts, subacute bacterial endocarditis prophylaxis clindamycin or quinolone Cephalosporins

9、Erythomycin Metronidazole quinolones,Drug sensitivity test,How to control the infection ?,Treatment plan 3 cefazolin (头孢唑林) 1.0 ivgtt. bid 3,Intraoral incision and drainage,Local treatment,Extraoral incision and drainage,Local treatment,Hints,According to the characteristics of bacterium According t

10、o the patients condition Combination use according to the indications ,Case #2,XXX, female, 68,- CT for SCC of FOM (T4N2M0),How to do?,XXX, female, 68 Oral ulcer for over half an year 55 Kg, loss weight 10kg in the past 4 months Heavy smoker and drinking for two decades Neck nodule found 2 months ag

11、o,Basic information,Whats else?,How to use of anticancer drugs?,Rational use,Drug sensitivity,Tumor type,imaging,Pathologic diagnosis,Site and size,TNM staging,Imaging,Q: CT (PET-CT) or MRI ?,MRI,Pathologic diagnosis,- SCC, moderately differentiated,H adriamycin 35 mg/m2 d5; 5-FU 500 mg d1-5, d21-28

12、; cyclophosphamide 600 mg + 5-FU 500 mg pre-surgery,Cisplatin adriamycin 5-FU,Yin M. J Oral Maxillofac Surg 2006,Regimen,40,PAF ICT,Immediate effects of PAF on primary tumors,Note: CR, complete response PR, partial response NC, no change PD, progressive disease FOM, floor of mouth,The clinical respo

13、nse rate (CR+PR) to PAF was 60.4%,41,Docetaxel 75 mg/m2 d1; Oxaliplatin 130 mg/m2 d2; 5-FU 500 mg/m2 d2-6, 21 days/cycle, 2 cycles.,Docetaxel Oxaliplatin 5-FU,Response: CR+PR 75.47% (40/53),Zhang D. Chin Med Eng 2012,Regimen,42,DOF ICT,Side-effect of DOF,Grade 3 and 4 leukopenia, including neutropen

14、ia, was significantly more prevalent in the docetaxel arms.,Events,Leukopenia Hypochromasia Thrombopenia Nausea Mucositis Neuritis Hepatic dysfunction Kidney dysfunction Alopecia,Rates (%),79.25,100.00,43,3. Recommendation: Docetaxel+cisplatin+fuorouracil (TPF),256 patients with untreated stage III-

15、IVA OSCC Docetaxel 75 mg/m2 d1; cisplatin 75 mg/m2 d1; 5-FU 750 mg/m2 d1-5, continuous infusion; 21 days/cycle, 2 cycles Followed by radical surgery and postoperative radiotherapy versus up-front radical surgery and postoperative radiotherapy The primary end point was overall survival (OS); Secondar

16、y end points included local control and safety,Courtesy of Zhang ZY, et al. the 9th Peoples Hospital, Shanghai, China,RCT (phase III) Regimen,44,CONSORT diagram,Follow-up 30 months,primary end point,45,Fig 2. (A) Overall and (B) disease-free survival in the control and experimental arms. TPF, doceta

17、xel, cisplatin, and fluorouracil.,There was no significant difference in OS and DFS between the control and experimental arms,OS,DFS,46,There was no clear benefit from induction chemotherapy in any of the subgroups, with the exception of patients with cN2 disease, who seemed to have improved OS and

18、DMFS when treated with induction chemotherapy,Patterns of Failure and Subgroup Analysis,The clinical response rate (CR+PR) to induction chemotherapy was 80.6%,47,Subgroup analysis of overall and diseasefree survival in the control and experimental arms. HR, hazard ratio; M/P, moderately/poorly.,Indu

19、ction chemotherapy improved overall survival in patients with Clinical N2 disease,48,(B) Subgroup analysis of locoregional recurrencefree and distant metastasisfree survival in the control and experimental arms. HR, hazard ratio; M/P, moderately/poorly.,Induction chemotherapy improved distant metast

20、asis-free survival in patients with Clinical N2 disease,49,The most frequent AEs - alopecia (70.5%) - nausea and/or vomiting (55.7%) - hematologic toxicity (28.7%) - altered liver function tests (19.7%),Adverse events (AEs),50,Meta-analysis (a),Study flow diagram,51,Forest plot of hazard ratios for

21、overall survival and 95% CI in fourteen randomized controlled trials in patients with resectable head and neck squamous cell carcinoma treated with induction chemotherapy followed by locoregional treatment, or locoregional treatment alone.,There was no significant difference in overall survival betw

22、een patients treated with and without induction chemotherapy (p = 0.84), neither was there a significant difference according to the protocol of induction chemotherapy, such as PF, other platin-containing combinations, or multiple agents without platin.,Forest plot of hazard ratios for overall survi

23、val and 95% CI in fourteen randomized controlled trials in patients with resectable head and neck squamous cell carcinoma treated with induction chemotherapy followed by locoregional treatment, or locoregional treatment alone.,52,Forest plot of hazard ratios for disease-free survival and 95% CI,For

24、disease-free survival, there was no significant difference between the patients treated with or without induction chemotherapy (p = 0.76),53,Forest plot of hazard ratios for distant metastasis-free survival and 95% CI in patients with resectable HNSCC treated with induction chemotherapy followed by

25、locoregional treatment, or locoregional treatment alone,Among 700 patients who developed distant metastases, those treated with induction chemotherapy had a significantly lower 5-year rate of distant metastases (8% difference, p = 0.02), compared to those treated without induction chemotherapy,54,Me

26、ta-analysis (b),Study flow diagram,Ma J, et al. Oral Oncology (2012),Induction chemotherapy decreases the rate of distant metastasis in patients with head and neck squamous cell carcinoma but does not improve survival or locoregional control: A meta-analysis,55,Five major sets of regimens were compa

27、red,Among the 40 eligible trials, 28 trials (4189 patients) receiving locoregional treatment with or without induction chemotherapy (IC) were included,IC + LRT versus LRT alone IC + RT versus CCRT or alternating CT and RT IC + CCRT versus CCRT alone IC + RT versus CCRT alone IC + RT versus surgery +

28、 RT,LRT, locoregional treatment CT, chemotherapy RT, radiotherapy CCRT, radiation and concomitant chemotherapy,56,Forest plot of comparison: induction chemotherapy followed by locoregional treatment versus locoregional treatment alone for all studies, outcome: 5-year distant metastasis.,Notably, 816 patients from 6 RCTs were assessed for 5-year distant metastasis rate, the patients receiving induction chemotherapy followed by locoregional treatment had a significantly lower metastasis rate than those receiving loco-r