Chemoradiotherapy for advanced head and neck cancer — Analysis of a prospective, randomized trial

Objective: To study the efficacy of neo-adjuvant chemotherapy followed by radiotherapy in advanced head and neck cancer.Study design: Randomised, prospective study.Setting: Tertiary academic referral center.Patients: One hundred and eighty patients of advanced head and neck squamous cell carcinoma.Intervention: Patients were randomized into two arms. The study arm (CT-RT arm) received 3 cycles of anterior chemotherapy with Inj. Cisplatin 100 mg/m² on D₁ and Inj 5F.U. 700 mg/m² on D₁-D₄ at an interval of 21 days, followed by external radiation. The control arm (RT arm) received external radiotherapy only. The dose of Radiotherapy was 64 to 68 Gy in conventional fractionation.Results: Patients of CT-RT showed better tumour control locally than patients who received only RT. Toxicities were commoner in CT-RT arm but they were manageable. 5 year survival is higher in the CT-RT arm (21% vs 16%; p value> 0.05).Conclusion: Anterior chemotherapy with Cisplatin and 5F.U. is associated with good clinical response which is translated into increased survival along with acceptable toxicities.     

Paclitaxel with cisplatin in concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma

The aim of this study was to evaluate the efficacy and the toxicity of paclitaxel and cisplatin in patients in concurrent radiotherapy for locally advanced nasopharyngeal carcinoma, and to see whether such a regime would be better tolerated than high dose cisplatin plus fluoracil in Chinese patients. Thirty-one patients with locally advanced nasopharyngeal carcinoma were enrolled. Patients were scheduled to receive two courses of concomitant chemotherapy, starting on day 1 and then day 28 during radiotherapy (70–76 Gy in 35–38 fractions in 7–7.5 weeks). Chemotherapy was given by intravenous infusion, paclitaxel 120 mg/m² in 3 h, cisplatin 75 mg/m² (25 mg/m² days 1–3). Adjuvant therapy was paclitaxel 135 mg/m² in 3 h, cisplatin 75 mg/m² (25 mg/m² days 1–3) on weeks 3, 6, 9 after radiotherapy. All patients completed radiotherapy, but for concomitant chemoradiotherapy, 20 of the 31 patients completed the 2 cycles of chemotherapy, while the other 11 could only receive 1 cycle due to various reasons. The median follow-up was 40 months, 2 patients developed locoregional recurrences, one of whom in the cervical lymph nodes, the other in the nasopharynx. The 3-year overall survival rate was 83.9% and the distant metastasis rate at 3 years was 13.6%. Grade 3–4 toxicities were neutropenia 12.9%, anaemia 6.45%, thrombocytopenia 3.22%, severe arrhythmia 3.2%, and hypersensitivity reaction 3.2%. In conclusion, paclitaxel with cisplatin as concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma is feasible, safe, and might improve regional control and survival rates in Chinese patients.     

Final Results of a Randomized Trial Comparing Chemotherapy Plus Radiotherapy With Chemotherapy Plus Surgery Plus Radiotherapy in Locally Advanced Resectable Hypopharyngeal Carcinomas

After neoadjuvant chemotherapy, a routine conservative approach followed by salvage surgery was evaluated in terms of local control and survival in cases of advanced potentially resectable hypopharyngeal carcinoma. Between 1985 and 1989, 92 patients with T3 or T4-N0,N3 operable squamous cell hypopharyngeal carcinomas received three courses of neoadjuvant chemotherapy every 2 weeks involving a combination of cisplatin, 100 mg/m², on day 1 and fluoruracil, 1 g/m², on days 2 to 5, followed by total laryngopharyngectomy plus postoperative radiotherapy in 47 patients (arm A) or radiotherapy alone in 45 patients (arm B). Randomization was always performed prior to chemotherapy. The response rates of tumor and node to chemotherapy were, respectively, 67% in arm A versus 79% in arm B (P > 0.05) and 54% in arm A versus 73% in arm B (P > 0.05). Grade III or IV toxicity was similar, affecting 15% of patients and 7% of cycles in arm A versus 16% of patients and 6% of cycles in arm B. After a mean follow-up of 92 months, survival was statistically better (P = 0.04) in arm A (5-year overall survival, 37%; median survival, 40 months) than in arm B (19% and 20 months) because of a better local control rate (63% versus 39%; P < 0.01). Better results were obtained for mutilant surgery in terms of local control and overall survival, regardless of response to neoadjuvant chemotherapy.     

Concurrent chemoradiotherapy with cyclophosphamide,pirarubicin, and cisplatin for patients with locally advanced salivary gland carcinoma

Conclusion. This concurrent chemoradiotherapy with CPA, THP, and CDDP showed major antitumor activity with manageable toxicity as treatment of advanced salivary gland carcinoma patients. The high response rate (RR) justifies further evaluation of this chemoradiotherapy combination. Objectives. The aim of this study was to evaluate the efficacy and toxicity of a concurrent chemoradiotherapy using cyclophosphamide (CPA), pirarubicin (THP), and cisplatin (CDDP) in patients with locally advanced salivary gland carcinoma. Patients and methods. Seventeen patients with previously untreated stage III–IV salivary gland carcinoma were entered in this trial between January 2000 and September 2005. Chemotherapy consisted of CPA 400 mg/m² on day 1, THP 40 mg/m² by 6-h infusion on day 1, and CDDP 60 mg/m² by 2-h infusion on day 1. Radiotherapy (2.0 Gy/fraction/day, mean total dose: 67.2 Gy (64.0–72.0 Gy)) administered 5 days per week, was targeted to begin on day 1. Results. The RR was 76% (13/17) and the pathological complete response (CR) was 24% (4/17). The primary site CR was 29% (5/17) and metastatic lymph node CR was 33% (4/12). The 5-year survival rate was 70%. Neutropenia, leukocytopenia and mucositis were common adverse effects, but all 17 patients were assessable for toxicity.     

Combined chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF), and radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

We evaluated the recommend dose and efficacy of chemotherapy (CTx) and concurrent chemoradiotherapy (ConcCRTx) with docetaxel (DOC), cisplatin (CDDP) and 5-FU (TPF) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Patients underwent 2 cycles of chemotherapy with TPF. In ConcCRTx, radiation was targeted to begin on Day 1. We compared the efficacy of ConcCRTx and induction chemotherapy followed by radiation (CTx followed by RTx) with TPF. In CTx followed by RTx, radiation was targeted to begin 21 days after the end of CTx. The recommend dose of CTx with TPF was DOC 60 (Day 1), CDDP 70 (Day 4) and 5 FU 750 (Day 1-5) mg/ m2/ day and overall response rate of CTx with TPF was 95%. The recommended dose of ConcCRTx was DOC 50 (Day 1), CDDP 60 (Day 4) and 5-FU 600 (Day 1-5) mg/ m2/ day. Overall response rate of ConcCRTx and CTx followed by RTx with TPF were both 100%, and CR rate of them were 87% and 84% (p > 0.05). One-year survival rate of them were 69% and 95% (p < 0.05). More patients had distant metastasis in CTx followed by RTx than in ConcCRTx. Toxicity, such as mucositis, leukocytopenia and neutropenia, was higher in ConcCRTx than in CTx followed by RTx.     

Combined modality treatment with full-dose chemotherapy and concomitant boost radiotherapy for advanced head and neck carcinoma

The purpose of this study was to evaluate the feasibility and efficacy of a treatment concept combining three cycles of full-dose chemotherapy (CT) with concomitant accelerated uninterrupted radiotherapy (RT). Twenty-three patients (median age: 54 years, range: 35–70) with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were included. The primary tumor involved the hypopharynx (n=7), base of the tongue (n=10), nasopharynx (n=2) or upper esophagus (n=1) or its location was unknown (n=3). Treatment consisted of three cycles of chemotherapy (cisplatin 100 mg/m² on day 1; 5-FU 1,000 mg/m² per day for 5 days as a continuous infusion, preceded by amifostine 910 mg/m²), repeated every 3 weeks. Uninterrupted concomitant boost-accelerated RT (total dose of 70 Gy in 6 weeks) started together on day 1 of the second cycle. All but two patients received the full course of RT. Eighteen patients achieved complete remission (78%). At a median follow-up of 45 months the overall survival was 56% (95% c.i. 32–79%) and the loco-regional control 71% (95% c.i. 52–91%). Toxicity involved reversible renal insufficiency of grade II in 9 patients (39%) and neutropenic fever in 9 patients (39%). All patients suffered from moderate to severe mucositis (grade II/III), and 19 patients presented cutaneous toxicity grade III. Concomitant boost-accelerated RT combined with concurrent full-dose cisplatin/5-FU chemotherapy and amifostine is feasible with manageable, although substantial, toxicity. The overall survival of 4 years is promising. Newer regimens causing less acute mucosal and skin toxicity are needed.     

Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial)

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m² paclitaxel, 100 mg/m² cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56–70 Gy in 5.5–7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4–72.2%), after 42 months was 56.5% (95% CI, 44.2–68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9–55.0%); after 42 months, 41.3% (95% CI, 29.3–53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials. This trial was initiated and conducted by the German Larynx Organ Preservation Study Group (DeLOS) which was founded as collaboration between head and neck surgeons and radiation oncologists to focus on the role of multimodality treatment in advanced laryngeal and hypopharyngeal cancer in Germany.     

Comparison of sequential chemoradiation with radiation alone in the treatment of advanced head and neck cancers

Objectives: To compare locoregional control with alternating chemo radiation and radiation alone in patients with locally advanced head and neck carcinoma.Study Design: A prospective randomized study.Setting: Tertiary academic referral center.Patients: 50 patients of biopsy proven locally-advanced carcinoma of head and neck.Intervention: 25 patients were kept in Group I or study group (i.e. alternating chemo-radiation) and 25 patients in Group II or control group (i.e. radiation alone). In the study group, patients were given 3 cycles of chemotherapy (Cisplatin 20 mg/m^[2] and Inj. 5-FU 200mg/m^[2] from day 1–5 of each week) during weeks 1,5 and 9 alternated with radiation dose of 10Gy/week was given during weeks 2,3,4 and 6,7,8. In the control group, patients were given a total dose of 60Gy in 6 weeks.Outcome measures: The response rate at the primary site and nodal site was better in study group as compared to control group.Results: On comparing the response at the primary and nodal site together, 72% (18/25) patients of group I and 44% (11/25) patients of group II showed CR. PR was seen in 28% (7/25) and 36% (9/25) patients in group I and II respectively. No response was seen in 5/25 (20%) of patients in Group II.Conclusion: Our study has revealed that alternating/ sequential chemoradiation is a promising and feasible approach for patients in advanced head and neck cancer.     

Randomized comparison of two chemotherapy, radiotherapy schemes for stage III and IV unresectable squamous cell carcinoma of the head and neck.

Between August 1983 and December 1986, 116 previously untreated patients with squamous cell carcinoma of the head and neck were randomized to receive induction chemotherapy followed by radiotherapy given in conventional fractions (55 patients, arm A) or an alternating chemotherapy and radiotherapy (3 courses of 20 Gy, 10 daily fractions each; 61 patients, arm B). The same chemotherapy was used in both arms: 6 mg/m2 vinblastine sulfate, hour 0; 30 mg bleomycin, hour 6; 200 mg methotrexate, hours 24 to 26; 45 mg leucovorin, hour 48. Forty-five patients had stage III disease and 71 had stage IV disease. All patients were evaluated for survival, 112 for toxicity, and 105 for analyses of response and time from the start of treatment until progression of disease. At the end of the combined treatment, we observed an overall response rate of 52% in arm A and an overall response rate of 64.9% in arm B. The incidence of mucositis was more relevant in arm B compared to arm A (P less than .00004). The difference in complete response, progression-free survival, and survival was statistically significant, with an advantage for arm B (P less than .03, P less than .02, and P less than .03, respectively). The analysis at a median follow-up of 36 months (range = 19 to 59) demonstrates a higher effectiveness for the alternating program.     

Induction chemotherapy by superselective intra-arterial high-dose carboplatin infusion for head and neck cancer

To evaluate the feasibility, maximum dose of drug tolerated, technical problems, systemic and local toxicity, response rate, overall and disease-free survival, we studied superselective intra-arterial infusion of high-dose carboplatin as part of a multimodality treatment for head and neck cancer. Forty patients with untreated stage II–IV head and neck squamous cell carcinomas received induction chemotherapy with high-dose carboplatin (three cycles at 2-week intervals using 300–350 mg/m² per cycle), delivered via superselective transfemoral angiography followed by radiotherapy or surgery plus radiotherapy. No technical complications occurred during or after the infusion. Systemic toxicity was minimal, and local toxicity was moderate. At the end of chemotherapy the overall complete and partial response rate was 90% (36/40) at the primary site and 64% (16/25) at the neck nodes. The median follow-up was 24.4 months (range 3–52). To date 21 patients are alive without disease, 2 are alive with disease, 13 have died of disease, and 4 have developed a metachronous lung tumor. There was a good correlation between the response to chemotherapy and disease-free survival. No statistically significant benefit in survival was observed with respect to other series of head and neck tumors treated with different protocols. However, discriminating between responding and nonresponding patients, this procedure can have a prognostic significance in planning integrated treatments for these types of tumors. Received: 14 January 1999 / Accepted: 2 July 1999     

Therapeutic efficacy of selective intraarterial chemoradiotherapy with docetaxel and nedaplatin for human papilloma virus-negative oropharyngeal cancer

ObjectiveHuman papilloma virus-negative oropharyngeal cancer has not achieved satisfactory outcomes compared with those of human papilloma virus-positive oropharyngeal cancer. This study evaluated the therapeutic efficacy of selective intraarterial chemoradiotherapy with the docetaxel and nedaplatin regimen for human papilloma virus-negative oropharyngeal cancer.MethodsTwenty-two consecutive patients with human papilloma virus-negative oropharyngeal cancer who had undergone selective intraarterial chemoradiotherapy were retrospectively analyzed. The primary tumor and whole neck were irradiated (50 Gy). Subsequently, the primary site and metastatic lymph nodes were boosted by 20 Gy. The intraarterial chemotherapy regimen comprised a combination of nedaplatin (80 mg/m²) and docetaxel (60 mg/m²), which was initially administered at the start of radiotherapy and was given every 4 weeks for three sessions. Each intraarterial dose of an anticancer agent was determined according to the percentage of the tumor volume supplied by the target artery to the total tumor volume, which was intraoperatively measured via cone-beam computed tomography. The outcome measures were locoregional control, disease-free survival, and overall survival rates and adverse events. Statistical analyses were performed using the Kaplan–Meier method.ResultsThe median follow-up period was 59 (range, 15–103) months. The T stage was T1/T2 in 5 patients (23%), T3 in 5 patients (23%), and T4 in 12 patients (54%). Cervical lymph node metastasis was staged as ≥N2c in 7 (32%) patients. Complete response was achieved in all patients at the first imaging examination after intraarterial chemoradiotherapy. The 5-year locoregional control, disease-free survival, and overall survival rates were 96% (95% confidence interval, 0.72–0.99), 91% (95% confidence interval, 0.68–0.98), and 100% (95% confidence interval, not available), respectively. Regarding serious acute adverse events, grade 4 laryngeal edema and leukopenia were observed in 1 (5%) and 11 patients (50%), respectively. No other serious acute adverse events were observed.ConclusionSelective intraarterial chemoradiotherapy with docetaxel and nedaplatin has the potential to achieve favorable locoregional control, disease-free survival, and overall survival rates in human papilloma virus-negative oropharyngeal cancer.     

Prospektive Phase-II-Studie zur neoadjuvanten Radiochemotherapie fortgeschrittener, operabler Mundh?hlenkarzinome

PURPOSE: The purpose of simultaneous chemoradiotherapy is to increase local-regional control and to decrease the incidence of distant metastases. Regimens containing cisplatin/5-FU chemotherapy are widely accepted as standard treatment in advanced head and neck cancer. Most studies reported promising response and survival data, but also severe mucosal toxicity. In recent years the newly developed drug Taxol demonstrated interesting activity in head and neck cancer as a single agent as well as in combination drug regimens. In the present outpatient phase II trial, we investigated the combination of Taxol/carboplatin with 40 Gy radiotherapy in a neoadjuvant setting of operable stage III/IV squamous cell carcinoma of the oral cavity and oropharynx. PATIENTS AND METHODS: Fifty-three patients were enrolled in this trial during the period from May 1998 to October 2000 and received five cycles weekly of Taxol (40 mg/m2) and carboplatin (AUC 1.5) with conventional radiotherapy (40 Gy). Within 3-4 weeks after chemoradiotherapy resection of the primary tumor and the regional neck nodes was performed. RESULTS: Fifty-two patients were evaluable for toxicity and response. Complete response was observed in 31 of 52 patients (CR 60%), and partial remission was seen in 21 of 52 patients (PR 40%). In 30 of 52 patients complete pathologic response (pCR 58%) was documented in the resection specimens. The 1-, 2-, and 3-year overall survival rate was calculated as 84%. CONCLUSION: Our present results demonstrated impressive clinical and pathological response rates of concurrent Taxol/carboplatin and radiotherapy as a preoperative treatment modality in advanced oral and oropharyngeal cancer.     

Concurrent chemoradiotherapy with cyclophosphamide, pirarubicin, and cisplatin for patients with locally advanced salivary gland carcinoma

CONCLUSION: This concurrent chemoradiotherapy with CPA, THP, and CDDP showed major antitumor activity with manageable toxicity as treatment of advanced salivary gland carcinoma patients. The high response rate (RR) justifies further evaluation of this chemoradiotherapy combination. OBJECTIVES: The aim of this study was to evaluate the efficacy and toxicity of a concurrent chemoradiotherapy using cyclophosphamide (CPA), pirarubicin (THP), and cisplatin (CDDP) in patients with locally advanced salivary gland carcinoma. PATIENTS AND METHODS: Seventeen patients with previously untreated stage III-IV salivary gland carcinoma were entered in this trial between January 2000 and September 2005. Chemotherapy consisted of CPA 400 mg/m2 on day 1, THP 40 mg/m2 by 6-h infusion on day 1, and CDDP 60 mg/m2 by 2-h infusion on day 1. Radiotherapy (2.0 Gy/fraction/day, mean total dose: 67.2 Gy (64.0-72.0 Gy)) administered 5 days per week, was targeted to begin on day 1. RESULTS: The RR was 76% (13/17) and the pathological complete response (CR) was 24% (4/17). The primary site CR was 29% (5/17) and metastatic lymph node CR was 33% (4/12). The 5-year survival rate was 70%. Neutropenia, leukocytopenia and mucositis were common adverse effects, but all 17 patients were assessable for toxicity.     

Concomitant chemoradiotherapy in pyriform sinus carcinoma

OBJECTIVES: To test the effectiveness of concurrent chemoradiotherapy in patients with pyriform sinus carcinoma and to demonstrate the feasibility of an organ preservation approach. DESIGN: Clinical trial phase 2. SETTING: University Hospital Center, St-Etienne, France. PATIENTS: The study population comprised 46 male patients with resectable stage III and IV pyriform sinus carcinoma. METHODS: Two successive chemoradiation regimens were investigated. In protocol 1 (24 patients), carboplatin was given on days 1 through 5 and 28 through 33, with an area under the curve dose of 5 mg/mL for 1 minute per day and bifractionated radiotherapy (160 rad [1.6 Gy]/fraction) delivered on days 1 through 16 and 28 through 38. A treatment break was planned on days 16 through 27. In protocol 2 (22 patients), chemotherapy was given with the same dose of carboplatin on days 1 and 21, and fluorouracil (750 mg/m(2) per day) on days 1 through 7 and 21 through 28. Radiotherapy with a single fraction of 180 rad (1.8 Gy)/d was delivered during the first 2 weeks and then 150 rad (1.5 Gy) twice a day during the next 3 weeks. MAIN OUTCOME MEASURES: Patients were evaluated for tumor response, toxic reactions, and organ preservation and survival rates. Statistical analysis of disease-free survival and overall survival was performed using the Kaplan-Meier method. RESULTS: A complete response was noted in 21 (88%) of the 24 patients following protocol 1 and 16 (73%) of the 22 patients following protocol 2. After 2 years of follow up, 16 patients (67%) (protocol 1) and 12 patients (55%) (protocol 2) retained their larynx without evidence of disease. During therapy, 15 patients (63%) (protocol 1) and 19 patients (86%) (protocol 2) required unplanned hospitalization for toxic effects. The overall survival and disease-free survival rates at 2 years were 58% (protocol 1) vs 53% (protocol 2) and 39% (protocol 1) vs 41% (protocol 2) (P =.80), respectively. CONCLUSION: Concomitant chemotherapy and bifractionated radiotherapy, although toxic, leads to good locoregional control and therefore to a significant level of laryngeal preservation.     

Comparison of acute toxicities associated with cetuximab-based bioradiotherapy and platinum-based chemoradiotherapy for head and neck squamous cell carcinomas: A single-institution retrospective study in Japan

Conclusion: Grade ≥ 3 mucositis/stomatitis and inability to feed orally were problematic for patients undergoing cetuximab-based bioradiotherapy (BRT) as well as platinum-based chemoradiotherapy (CRT). Severe mucositis/stomatitis and radiation dermatitis should be addressed carefully in patients undergoing cetuximab-based BRT as well. Objectives: The efficacy of cetuximab-based BRT in locally advanced head and neck squamous cell carcinomas has been established. However, the safety of cetuximab-based BRT in comparison with platinum-based CRT is currently under investigation. Method: This study retrospectively analyzed 14 patients undergoing cetuximab-based BRT and 29 patients undergoing platinum-based CRT to compare the incidence of acute toxicities. In the BRT group, an initial cetuximab loading dose of 400 mg/m² was delivered 1 week before the start of radiotherapy. Seven weekly infusions of 250 mg/m² of cetuximab followed during the definitive radiotherapy. In the CRT group, cisplatin was administered at a dose of 40 mg/m² weekly during the definitive radiotherapy. Results: The BRT group had a higher incidence of Grade ≥ 3 radiation dermatitis than did the CRT group (43% vs 3%, respectively, p < 0.01). The incidence rate of Grade ≥ 3 mucositis/stomatitis was 64.3% and 41.4% in the BRT and CRT group, respectively (p = 0.1484), while the incidence rate of the inability to feed orally was 38.5% and 55.2%, respectively (p = 0.2053).     

Concurrent chemotherapy and radiotherapy as initial treatment for stage II supraglottic squamous cell carcinoma

Objective: To evaluate the efficacy and safety of concurrent carboplatin (CBDCA) and radiotherapy for laryngeal carcinoma, we investigated survival rates and laryngeal preservation rates in patients with this treatment modality and those with radiation therapy only. Methods: We underwent chemotherapy with CBDCA and conventional radiotherapy concurrently to 17 patients with untreated stage II (T2N0M0) supraglottic squamous cell carcinoma since November 1990. CBDCA (100 mg/m²) was administered intravenously once a week concurrently with radiotherapy (2.5 Gy/fr, 4 times a week). At the dose of 40 Gy, the results were evaluated, and some of the patients underwent planned surgery and others continued the radiotherapy up to 65 Gy. Results: Overall 5-year survival rate by Kaplan–Meier method was 81.1%. Actual laryngeal preservation rate was 76.0%. Toxicity over grade III was noticed in two patients. Compared with 14 cases of historical controls, which were treated by radiation therapy alone between 1988 and 1990, the cases with concurrent radiotherapy and chemotherapy had statistically significant advantage in overall successful laryngeal preservation rate (P<0.05), whereas the two groups were not significantly different in the overall 5-year survival rate.     

High-dose cisplatin concurrent to conventionally delivered radiotherapy is associated with unacceptable toxicity in unresectable,non-metastatic stage IV head and neck squamous cell carcinoma

Unresectable head and neck squamous cell carcinoma (HNSCC), non-metastatic, comprises a heterogeneous group of patients (pts), formed of stage III and IV pts. Since the available literature had not distinguished among these two groups, we prospectively addressed whether the recommended regimen involving cisplatin 100 mg/m² concurrent to conventionally delivered radiotherapy (RT) is feasible in stage IV pts, based on the efficacy and safety of this regimen. A total of 30 pts were enrolled onto this study. Chemoradiation (CRT) consisted of RT 70 Gy, delivered in 35 daily fractions of 2 Gy, in 7 weeks, concurrent to cisplatin 100 mg/m² on days 1, 22 and 43. Supportive treatment was provided as needed. Twenty-eight pts had tumors staged as T4 and 20 had N2 or N3 cervical involvement. The most common primary sites were the oral cavity and the oropharynx (23 pts). We observed six complete responses and 12 partial responses, with an overall response rate of 60%. A high rate of treatment-related toxicities was observed, with three deaths during CRT, and 26 pts suffering from one or more grade 3/4 toxicities, mainly dysphagia, mucositis, dermatitis, vomiting, infection or anemia. A prolonged treatment time was observed (63 days), as a result of unplanned treatment breaks. The lack of requirement of red blood cell transfusion was favorably related to the response to the treatment (93% vs. 50%, P = 0.033). For the whole population, with a median follow-up of 20.8 months, the median progression-free survival (PFS) was 8.0 months, and the median overall survival (OS) was 17.3 months. Longer median PFS and OS were seen in responding pts (12.8 vs. 4.1 months, P = 0.0001; and not reached (NR) vs. 10.4 months, P = 0.0037, respectively), as well as in those pts not requiring red blood cell transfusion (12.8 vs. 3.9 months, P = 0.0162; and NR vs. 10.4 months, P = 0.0176, respectively). In conclusion, this concurrent CRT regimen is hardly delivered in stage IV, unresectable, locally advanced HNSCC pts, due to treatment-related toxicities and longer RT duration. As a subset of pts may benefit from this regimen, adequate patient selection and aggressive supportive measures are essential.     

Concurrent chemoradiotherapy for head and neck squamous cell carcinoma with indication of total laryngectomy

Subjects were 15 patients--13 men and 2 women--with squamous cell carcinoma of the head and neck, indicating total laryngectomy. Their median age was 62 years, ranging from 50 to 71 years. Three had stage III disease and 12 stage IV disease. These patients were treated with concurrent chemoradiotherapy and had been followed up for more than 2 years from the start of treatment. Primary sites were hypopharynx in 7, larynx in 6, or oropharynx in 2. Treatment consisted of 5-Fluorouracil (5-FU) on cis-platinum (CDDP). 5-FU was given at 1000 mg/m2 per day as continuous infusions during 4 days, and 60 mg/m2 of CDDP was given on day 4 beginning on day 1 and 35 of a concurrent chemoradiotherapy course. Radiation was given in single daily fractions of 2 Gy and 5 fractions per week to a total dose of 60 to 70 Gy. Radiation break was scheduled from day 26 to 35. The median total delivered dose of radiation was 66 Gy. Toxicities included mucositis (grade 3, 33.3%, grade 4, 13.3%), vomiting (grade 3, 33.3%), leukopenia (grade 3, 20%). Twelve PT (80%) received scheduled treatment. Seven (46.7%) had clinical complete response and 8 (53.3%) partial response. Median overall survival was 27.2 months (5.6-33.9 m) and progression-free survival was 26.5 months (5.6-33.9 m). The larynx was preserved and free of disease in 60% of patients overall. Two-year overall survival (OS) was 71.8% and progression free survival (PFS) rates was 60%. Failure patterns showed 5 with locoregional recurrence and 1 with distant metastasis. Concurrent chemoradiotherapy improved two-year OS and PFS compared to radiotherapy alone with a significant difference. Concurrent chemoradiotherapy is thus effective in preserving the larynx in a high percentage of patients and improving two-year OS and PFS rates without compromising QOL.     

EGCG对鼻咽癌细胞株裸鼠移植瘤的放疗增敏作用以及对Survivin表达的影响

目的研究凋亡抑制基因Survivin的表达与EGCG对鼻咽癌CNE 2裸鼠移植瘤放疗增敏作用的关系。方法将低分化鼻咽癌细胞CNE 2接种于4～6周龄的雌性裸鼠皮下,待移植瘤生长至4～6?mm时,随机分为4组,分别采用NS、EGCG［50?mg/(kg·w）］、放疗（15?Gy）、EGCG给药24?h后再行放疗等方法分别处理各组裸鼠,处理前后分别测量裸鼠移植瘤的短径、体积。21?d后处死裸鼠,取出肿瘤并称重,将肿瘤组织分成两份,分别用来进行病理切片TUNEL染色以及RT PCR检测Survivin mRNR的表达。结果EGCG＋放疗对裸鼠移植瘤的生长抑制最为明显,肿瘤生长抑制率为89.3%,消退率为40.0％。与对照组EGCG组、放疗组相比,EGCG＋放疗组的凋亡指数均明显增加（P＜0.05),同时,伴有Survivin mRNR的表达显著下降（P＜0.05）。结论EGCG对鼻咽癌裸鼠移植瘤可能具有放疗增敏作用,这种作用可能与凋亡抑制基因Survivin的表达下调有关。