RESPONSE AND SIDE EFFECTS STATUSES 1. Response to neo-adjuvant chemotherapy

Chemotherapy regimen

Pre-operative chemotherapy was usually applied for advanced cancers of head, face and neck. Initial studies used CF regimen. Then, some authors added taxane (docetaxel and palitaxel) to CF regimen to make TCT regimen. This new regimen showed a higher response rate, but also more side effects. In Vietnam, most patients had average BMIs, poor intakes and were difficult to tolerate a 3-drug regimen. So, cisplatin combined with taxane (docetaxel and palitaxel) could help patients achieve high response rates and good tolerances.

General response rate by chemotherapy cycles

In our study, all patients received full treatments for 3 cycles. Response status was increased gradually by chemotherapy cycles. After 3 cycles, complete response rate was 14.4%, parital response rate accounted for 36.8%, non-remission rate was 36.8%;

progressive disease accounted for 4.8%. Till now, no author in Vietnam has reported neo-adjuvant chemotherapy result by this regimen, however, some studies for other regimens for patient-group like ours were did. According to Le Van Quang’s result of CF regimen study, complete response rate was 12%, parital response rate accounted for 50.4%, non-remission rate was 30.8%; progressive disease accounted for 6.8%. Salama et al. did a Phase-II study on 222 patients with recurrent and metastatic head and neck cancer at stages III and IV (M0) treated by TC regimen followed by simultaneous chemotherapy and radiotherapy for radical treatment, his result showed that complete response rate was 75%.

Similarly, Vokes (2003) showed a complete response rate after using neo-adjuvant TC chemotherapy for 69 patients with recurrent and metastatic head and neck cancer in situ as 75.3%.

CF and TC are the most common 2-drug regimens. Both of them had high complete response rates, helping reduce sizes of tumor and lymph nodes, facilitate future surgery for radical treatment.

Response rate by disease’s stage

In our study, response rates after using 3 chemotherapy cycles for patients with stages III and IV disease were 64.8% and 55.7% respectively. There was a difference of response levels between stages T and N with p < 0.05. After doing a study on neo-adjuvant Paclitxel and Cisplatin regimen on patients with head and neck squamous cell carcinoma at stage IV, Stefano (2011) reported a response rate after 3 chemotherapy cycles of 74.4% for this stage. The author thought that his response rate was higher than that in some other studies due to more chemotherapy cycles used and higher dose for Paclitaxel on his study.

Designation of surgery after 3 chemotherapy cycles by disease’s stage

After 3 neo-adjuvant TC cycles, 66 patients were designated to receive surgery, accounting for 52.8%. So, pre-operative neo-adjuvant chemotherapy significantly contributed to reduce sizes of tongue tumor and cervical nodes to make surgery more easy.

In 2003, Licitra reported his study on 195 with oral squamous cell carcinoma, study’ result showed that neo-adjuvant chemotherapy helped reduce mandibulotomy rate [83].

Post-treatment cell degeneration

According to Zhong, patient-group with a good response on histopathology, that is only below 10% of cancer cells remained on their specimens, had overall and progression-free survivals higher significantly than those in poor-response group. Among 63 operated patients, 9 people had no cancer cell on their post-operative specimens, accounting for 14.3%. However, this result didn’t absolutely reflect histopathological response rate of the regimen because we didn’t do any re-biopsies for patient-group treated by post-chemotherapy radiation. Our study result was different from results of other authors, this

was due to our study only implemented on tongue squamous cell carcinoma, but not on other sites in the oral cavity.

4.2.2. Side effects

4.2.2.1. Side effects on hematology, liver and kidneys

Chemotherapy drugs didn’t only affect to cancer cells, but also normal cells of the body, especially cells having fast division speeds such as cells lining the digestive tract, hair cells, red blood cells, and white blood cells. This factor affected to patient’s treatment course and life quality, patients may be even died due to chemotherapy drugs.

Side effects on hematology Low hemoglobin

Among 375 patients treated by chemotherapy, 129 people got grade-1 low hemoglobin (34.4%), 48 patients had grade-2 low hemoglobin (12.8%). When doing a comparision with other studies, which also used TC regimen or other 2-drug regimens or even 3-drug TCF regimens, results were similar.

Rajesh et al (2018) also studied 70 patients with stage T4 oral cancer, 56 people were treated by TC regimen, his result showed that only 2 patients had low hemoglobin at grade 3 or 4 (3.6%).

Stefano et al (2011) studied 43 patients with recurrent and metastatic head and neck cancer at stage IV (M0) from January, 1999 to December, 2002 by neo-adjuvant TC chemotherapy regime. After 3 cycles, 10 patients had low hemoglobin at grades 1 and 2 (23.3%), and no patient had low hemoglobin at grade 3 or 4. Therefore, TC regime helped reduce side effect of low hemoglobin.

Leukopenia

Before treament, all patients had normal leukocyte and granulocyte counts, but during taxane and cisplatin combination regimen, grade-3 leukopenia occured on 91/375 cycles, accounting for 24.3%. Grade-4 leukopenia rate was 9.3%. Grade-3 leukopenia rates on courses I, II and III were 29.6%; 20.8% and 22.4 respectively. Grade-4 leukopenia rates on courses I, II and III were 9.6%; 10.4% and 8.0% respectively. Leukopenia rates at grades 3 and 4 were 25.3% and 24.8% respectively (caculated by 375 cycles).

Gibson (2005) stated that TC regimen had a lower side effect of leukopenia compared to that of CF regimem. So, leukopenia rate at our patient-group treated by TC regimen was similar to results of other author around the world, and was lower than CF patient-group.

Thrombocytopenia

In our study, thrombocytopenia rate after 3 cycles was 14.1% (rates of patient with stages 1 and 2 thrombocytopenia were 13.9% and 0.2% respectively, no thrombocytopenia patient was at stage 3 or 4). Thrombocytopenia rate by each cycle:

cycle 1 (12.8%), cycle 2 (15.2%), cycle 3 (13.6%).

Another study by Basaran (2013), a study on using TC regimen on 50 patients with recurrent and metastatic recurrent and metastatic head and neck cancer, showed that

thrombocytopenia condition was uncommon, it mainly occured at grades 1 and 2 (3.9%

and 1% respectively), both thrombocytopenia rates at grades 3 and 4 were 1%. Gibson reported that rates of thrombocytopenia patient at grades 3 and 4 treated by TC regimen were 3% and 1% respectively. When comparing with CF, TC regimen had fewer thrombocytopenia. Thus, TC regimen also showed little side effect on thrombocytopenia, if any, it mainly occured at mild level, grades 1 and 2.

Toxicities on liver and kidneys

TC regimen rarely caused elevated liver enzymes. In our study, grade-II elevated SGOT was only seen in coruse I with a rate of 0.8%. Most pts had grade-I elevated SGOT.

Cisplatin caused a severe accumulation of side effects on the kidneys. However, our result showed that there was no patient with elevated creatinine level at grades 2, 3 and 4.

Grade 1 elevate creatinine level were 2.4%, 4.0% and 7.2% at courses 1, 2 and 3 respectively. Foreign authors also reported similar results. According to Stefano et al.

(2011), TC regimen rarely caused side effects on liver and kidneys, there were no patient with elevated creatinine or liver enzyme level at grades 3 and 4. In general, side effects on hematology, liver and kidneys were few, no patient had life-threatening side effects.

4.2.2.1. Other side effects Vomiting and nausea

In the treatment regimen, antiemetic was designated during chemotherapy and for post-chemotherapy prophylaxis. Our result showed that rates of patients having grades I, II and III nausea were 31.2%; 20%; 21.6% respectively; no patient had a grade-4 nausea.

Rate of patients having grades I, II and III vomiting were 19.2%; 14.4%; 17.6%

respectively; no patient had a grade-4 vomiting.

Myalgia

Myalgia was often associated with a treatment using paclitaxel. However, this condition was usually mild. As in Adamo’s study (2003), only 5.8% of patients appeared this condition and all of them had grade-2 myalgia. Gibson’s study result (2005) showed that there was no patient with grades 3 and 4 myalgia in total of 108 patients treated by TC regimen. Our result was similar: myalgia condition mainly occured at grades I and II, accounting for 6.4% and 1.6%, respectively.

Side effects on the peripheral nervous system

Side effects on the peripheral nervous system mainly occured at grades I and II, accounting for 32.8% and 4.8% respectively. There was patient with grade III or IV side effects. Stefano’s study result also showed that rate of patients having side effects on peripheral nervous system was 11.6%, of which there were only 2 patients with grade 3 side effects and no patient had grade 4 side effects. In Gibson’s study, there was no patients having side effects on the peripheral nervous system at grade 4, while grade 3 rate was 5%.

These side effects were often associated with a treatment using paclitaxel. Patients were advised something about lifestyle to minimize these effects, such as keeping warm the body, avoiding exposure to cold temperatures, including refrigerators and air conditioners, drinking warm water, and using protective equipment.

4.3. Overall survival