• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.sup3
• /
• pp.87-91
• /
• 2016

To investigate whether excision repair cross complementing-group1 (ERCC1) expression status could serve as a bio-predictor of response to platinum-based induction chemotherapy for head and neck cancers (HNCs) patients with a diagnosis of epithelial HNC were studied retrospectively. Paraffin embedded tumor samples of the patients were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) to determine ERCC1 expression status and its correlation with response to platinum-based induction chemotherapy was investigated. Of 44 included patients, 33 were male (75%) and 11 were female (25%) with a mean age of 53 years. Some 36% of patients whose tumor samples had high ERCC1 expression showed no response to induction chemotherapy. The value for patients with low ERCC1 expression was 9% and the difference was statistically significant (p=0.03). The ERCC1 expression state did not significantly vary between patient groups according to sex, age, primary tumor site, and tumor and node stage. Our study indicates that ERCC1 expression status detected by RT-PCR might serve as a bio-predictor of response to platinum-based induction chemotherapy for epithelial HNCs.

• Radiation Oncology Journal
• /
• v.16 no.3
• /
• pp.283-289
• /
• 1998

Purpose : This study was performed to analyze the efficacy of induction chemotherapy fellowed by radiation therapy in locally advanced non-small cell lung cancer Materials and Methods : Eighty patients with locally advanced non-small cell lung cancer treated from 1989 to 1995 at Pusan Paik hospital were analyzed retrospectively. Twenty-one patients were treated with induction chemotherapy followed by radiation therapy and Fifty-nine Patients were treated with radiation therapy alone. Chemotherapy regimen consisted of cisplatin-based combination (2 or 3 drugs). All patients were treated by Co-60 or 6 MV linear accelerators. Radiation dose ranged from 50 Gy to 80 Gy (median 64.8 Gy). We evaluated response rate, survival rate, and pattern of failure in both treatment groups. Results : Overall response rate in induction chemotherapy group and radiotherapy alone group were 48% and 45%, respectively. Of the 80 patients, 46 patients were evaluable for pattern of failure. Initial failure pattern in induction chemotherapy group was as follows: 8 (67%) at locoregional, 4 (33) in distant metastasis. Radiation alone group was 21 (71%) and 5 (29%), respectively. Results showed no difference of distant failure between induction chemotherapy group and radiation alone group. The 1 and 2 year survival rate in induction chemotherapy group were 43% and 14%, respectively and in radiotherapy alone group, 31% and 7%, respectively (p=0.135). Conclusion : In stage III non-small cell lung cancer, induction chemotherapy and radiation therapy showed increased tendency in survival with no statistical significance Induction chemotherapy seems to have no effect of decreasing distant failure and no survival advantage compared with radiotherapy alone.

• Korean Journal of Head & Neck Oncology
• /
• v.17 no.1
• /
• pp.32-37
• /
• 2001

Objectives: We performed this study to compare the short term results of induction chemotherapy and radiotherapy versus concurrent chemoradiotherapy in patients with locally advanced head and neck cancer. Materials and Methods: From Oct. 1985 to May 1998, 121 patients with locally advanced head and neck cancer were treated with induction chemotherapy and radiotherapy (induction group) or concurrent chemoradiotherapy (concurrent group), and a retrospective analysis was done. Induction chemotherapy was done for 97 patients, and concurrent chemotherapy for 24 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Primary site showed nasopharynx(72.2%), oropharynx(27.8%) in induction group, and nasopharynx(50%), oropharynx(50%) in concurrent group. Chemotherapy regimen was CF(cisplatin and 5-fluorouracil) for 67 patients and CVB (cisplatin, vincristine, bleomycin) for 30 patients in induction group, and CF for all of 24 patients in concurrent group. Proportion of patients treated with more than 2 cycles of planned chemotherapy was 94.8% in induction group and 87.5% in concurrent group. Conventionally fractionated radiotherapy with daily fraction size of 1.8-2.0Gy and 5 fractions/week was done. Total dose was 61-95Gy (median 73.4Gy) for induction group, and 69.4-75.4Gy (median 69.4Gy) for concurrent group. Follow-up time was 4-161 months (median 38 months) for induction group, 7-35 months (median 21.5 months) for concurrent group, respectively. Results: According to treatment modality, overall 2-year survival rates were 68.0% for induction group, 74.3% for concurrent group (p>0.05). two-year disease-free survival rates were 51 % and 74% (p=0.05). Complete response rates were 67.4% for induction group and 83.3% for concurrent group (p=0.09). The incidence of grade 3-4 hematologic toxicity (2.1% vs. 25%, p=0.001) and grade 3-4 mucositis (9.3% vs. 37.5%, p=0.002) during radiotherapy was higher in concurrent group. Conclusion: Concurrent chemoradiotherapy showed a trend of improvement in short-term survival and treatment response when compared with induction chemotherapy and radiotherapy in locally advanced head and neck cancer. A more controlled randomized trial is needed.

• Radiation Oncology Journal
• /
• v.8 no.2
• /
• pp.207-212
• /
• 1990

To determine the correlation between the response to induction chemotherapy and subsequent radiotherapy we analyzed the clinical records of 60 patients with locally advanced carcinoma of the head and neck retrospectively who had completed a full course ($2\~3$ cycle) of induction chemotherapy and curative radiotherapy in Korea Cancer Center Hospital between 1986 and 1989. Chemotherapy was administeredd with CDDP+Bleomycin (BP) in 20, CDDP+5-FU (FP) in 37, and hybrid of BP and FP in three patients. Radiotherapy was giver conventionally with a dose of 65 to 75 Gy or more over seven to eight weeks according to the size of lesion. Response rates following induction chemotherapy were $80\%$ for the tumors and $879\%$ for the nodes whereas complete reponse rates were $12\%\;and\;13\%$, respectively. Six months after radiotherapy $67\%$ of the tumors and $77\%$ of the nodes achieved a complete response. Among the 48 tumor responders and the 31 nodal responders to chemotherapy,39 ($81\%$) and 28 ($90\%$), respectively, achieved complete response after radiotherapy. Thus, whether or not the tumor and node respond to induction chemotherapy was predictive of the response to subsequent radiotherapy (p<0.0005 in tumor, p<0.0001 in node). By reanalyzing according to disease subsets (i.e. primary site, T-stage, N-stage) this relationship was not observed at T1-T2 disease (p>0.3). Therefore the tumor or node's response to induction chemotherapy is a predictor for subsequent radiotherapy except in T1-T2 tumors, and complete response to radiotherapy can be expected despite the failure of induction chemotherapy in $T_1-T_2$ tumors.

• Radiation Oncology Journal
• /
• v.11 no.2
• /
• pp.295-301
• /
• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.

• Korean Journal of Head & Neck Oncology
• /
• v.24 no.1
• /
• pp.26-32
• /
• 2008

Purpose：Hypopharyngeal carcinoma is usually diagnosed as an advanced disease after an asymptomatic beginning, and it is related to a high frequency of lymph node metastases. An eventual negative outcome may occur not only because of possible locoregional failures but also for frequent distant metastases. Thus, the efficacy of induction chemotherapy followed by radiation therapy, with regards to the response, survival rate and complications for locally advanced hypopharyngeal carcinoma patients, was examined. Methods and Materials：Since July 1998 to February 2001, 18 patients having locally advanced hypopharyngeal carcinoma were treated with induction chemotherapy followed by radiation therapy, and the results were retrospectively analyzed. The regimen of the induction chemotherapy was the 5-flurouracil(5-FU, 1,000mg/$m^2$ daily for 5 consecutive days) and cisplatin(100mg/$m^2$ on day 1) combination at 3-week intervals for 2 cycles. The total radiation dose for the primary tumor and metastatic lymph nodes was 68.4-72.0Gy(median：70.2Gy) Results：The 3-year overall survival rate and disease free survival rate were 31.3% and 22.2%, respectively. In 6 patients(33.3%), preservation of the larynx for over 3 years was possible. After the induction chemotherapy and radiotherapy, a complete response was noted in 14 patients(77.8%), and a partial response in 4 patients (22.2%), with an overall response rate of 100%. Conclusion：Induction chemotherapy followed by radiation therapy is an effective treatment and larynx preservation rate was 33% in patients with locally advanced hypopharyngeal carcinoma in our report.

• Korean Journal of Head & Neck Oncology
• /
• v.6 no.1
• /
• pp.11-23
• /
• 1990

Systemic chemotherapy is usually regarded as the standard treatment for palliation in patients with recurrent or metastatic cancer who have failed the definite local treatment with surgery and/or radiotherapy. Recently, with the introduction of more active chemotherapeutic agents and combinations, systemic chemotherapy is being increasingly used before or after local therapy in patients with previously untreated locally advanced head and neck cancer. The most active agents for the head and neck caner are methotrexate, 5-fluorouracil (5-FU), cisplatin and bleomycin. The overall response rates to each of these four drugs are 15-30% expecially when used as first line therapy. But most of these responses are partial with a mean duration of 3-5 months. Various combinations with methotrexate, 5-FU, cisplatin, and bleomycin have been tried with overall response rates of 50-90%, and 10-20% of complete responses. The introduction of chemotherapy prior to local therapy, induction chemotherapy, has been investigated with improved survivals in patients with complete response, especially pathologic, though improvement in overall survival has not been proved yet after the induction chemotherapy. Other therapeutic modalities, such as 'Sandwich' chemotherapy between surgery and radiotherapy, concomittent chemo-radiotherapy and post local treatment adjuvant chemotherapy have been pursued with some hopeful results but these trials should be compared with prospective randomized Phase III trials. To increase the response rates and enhance the survival, important work still remains; 1. Identification of better prognostic factors, 2. Improvement in staging, 3. Development of more active and safter chemotherapeutic agents, 4. Identification of the proper sequence for the addition of chemotherapy to multimodality treatment, and 5. Testing the value of such chemotherapy in locally advanced cancer patients.

• Korean Journal of Head & Neck Oncology
• /
• v.20 no.2
• /
• pp.172-176
• /
• 2004

Background and Objectives: Standard treatment of locally advanced laryngeal, hypopharyngeal, and some oropharyngeal cancers includes total laryngectomy. In an attempt to preserve the larynx through induction chemotherapy, we designed induction chemotherapy followed by definitive radiation in patients with potentially respectable head and neck cancer to determine whether organ preservation is feasible without apparent compromise of survival. Materials and Methods: The twenty-six patients diagnosed advanced head and neck squamous cell carcinoma, Stage III or IV (AJCC 2002) and performed organ preservation protocols in Ajou university hospital from 1994 to 2001 were included in this study. Results: Neoadjuvant chemotherapy showed an overall response rate of 84.6% and a complete remission (CR) rate was 59.1% following neoadjuvant chemotherapy and radiation. Seven of thirteen patients were able to preserve their larynges for more than two years by chemotherapy and radiation. There were no treatment related mortality after 2 cycles of induction chemotherapy. Conclusion: Although Organ preservation protocol through neoadjuvant chemotherapy and radiation need more controlled randomized study, it was considered alternative treatment modality in advanced head and neck cancer.

• Radiation Oncology Journal
• /
• v.22 no.4
• /
• pp.247-253
• /
• 2004

Purpose: Hypopharyngeal cancer is diagnosed at the advanced stage in most cases, which the prognosis known to be poor. Thus, the efficacy of induction chemotherapy followed by radiotherapy, with regards to the response and survival rate for stage IV hypopharyngeal cancer patients, was examined. Materials and Methods: From July 1998 to February 2000, 18 cases were diagnosedas AJCC stage IV hypopharyngeal cancer without distant metastasis. These patients were treated with induction chemotherapy followed by radiotherapy, and the results retrospectively analyzed. The regimen of the induction chemotherapy was the 5-FU and cisplatincombination, at 3-week intervals for, 2 cycles. The total radiation dose for the primary lesion and metastatic lymph nodes was $68.4\~72.0$Gy (median: 70.2 Gy). Results: The: The median follow up period was 28 months, ranging from 7 to 99 months. The 3-year overall survival and disease-free survival rate were 41.7 and $31.1\%$, respectively. In 6 cases ($33.3\%$), conservation of the larynx for over 3 years was possible. After the induction chemotherapy there were 16 partial responses ($88.8\%$), 1 complete response and 1 with no response ($5.6\%$ each), therefore, 17 of the 18 cases ($94.6\%$) showed responses. After the completion of the induction chemotherapy and radiotherapy, a complete response was noted in 13 cases ($72.2\%$), a partial response in 5 ($27.8\%$), with an overall response rate of $100\%$. In the analysis of the prognostic factors influencing the survival rate, the 3-year and disease-free survival rates for the complete and partial response groups were 43.1, and $20.0\%$, and 39.6, and $20.0\%$, respectively (p=0.0003, p=0.002). Only the final response after treatment completion was statistically significant. Conclusion: For stage IV hypopharyngeal cancer, induction chemotherapy followed by radiotherapy was an effective treatment, with no severe side effects.

• Korean Journal of Head & Neck Oncology
• /
• v.22 no.2
• /
• pp.123-129
• /
• 2006

Objective ： This retrospective study was designed to evaluate the anti-tumor efficacy and toxicities of the radiation therapy(RT) combined with cisplatin-based chemotherapy in locally advanced nasopharyngeal cancer(NPC). Materials and Methods ： Fifty three patients with locally advanced NPCs(AJCC stage II, III, IV) received curative RT and cisplatin-based chemotherapy. Duration of follow-up ranged from 5.5 to 201 months(median 50.8 months). Nineteen patients(35.8%) were treated with induction chemotherapy including cisplatin $100mg/m^2$ for 1 day and 5-fluorouracil $1g/m^2$ for 5 days followed by RT(Induction CTx-RT). Another 34 patients (64.2%) were treated with concurrent chemoradiation(CCRT) using cisplatin $100mg/m^2$(D1, 22, 43). Results ： Thirty-six(67.9%) and 11(20.8%) patients achieved clinical complete response and partial response, respectively. The pattern of failure was as follows：14 locoregional recurrence(26.4%) and 7 distant metastasis(13.2%). Among them, two patients(3.8%) had both locoregional and distant failure. Median overall survival(OS) and progression-free survival(PFS) were 85.5 months and 87.5 months, respectively. Five-year OS rate was 57.1%. The stage(AJCC), tumor response to chemoradiation and T stage were significant prognostic factors for OS(p=0.0113, p=0.0362 and p=0.0469). The stage(AJCC), tumor response to chemoradiation were also significant prognostic factors for PFS(p=0.0329, p=0.0424). Compared to each treatment group(Induction CTx-RT vs. CCRT), there were no significant differences in OS and PFS(p=0.7000, p=0.8261). Grade 3-4 mucositis, nausea/vomiting and hematological toxicities were noticed in 35.8%, 11.3% and 13.2%, respectively. Delayed RT over 2 weeks was inevitable in 26.5%. Seventeen patients(50%) successfully completed planned 3 courses of cisplatin in CCRT group. Conclusions ： RT combined with cisplatin-based chemotherapy in locally advanced NPC showed high response rate, good locoregional control, and survival rate. As expected, frequency of acute toxicities increased, and the patient's compliance to treatment was need to be improved. Although our data could not show additional survival benefit of CCRT compare to that of induction chemotherapy followed by RT, patients' accrual and further follow-up are required due to limitation of retrospective study.