Sadamoto Zenda

Weekly paclitaxel as second-line chemotherapy for advanced or recurrent gastric cancer

BackgroundPaclitaxel scheduled every 3 weeks has shown a response rate of ∼20% for gastric cancer, with modest hematological toxicity. Weekly administration of paclitaxel in patients with breast or ovarian cancer has shown equivalent efficacy and milder toxicity compared with an every-3 week schedule. We investigated, retrospectively, the antitumor effects and toxicity profiles of weekly paclitaxel for patients with metastatic or recurrent gastric cancer in clinical practice.MethodsIn 38 patients who had metastatic or recurrent histologically confirmed gastric cancer and a history of one prior chemotherapy regimen, other than paclitaxel or docetaxel, paclitaxel (8mg/m2) was administered weekly, three times every 4 weeks, with short-term premedication.ResultsAll 38 patients had had prior chemotherapy that included 5-fluorouracil, the fluoropyrimidine anticancer drug S-1, or cisplatin. The median number of courses in the present regimen was 6 (range, 1–44+). Dose intensity was 5mg/m2 per week, corresponding to 92% of the planned dose (6mg/m2 per week). The overall response rate was 24% (6/25) in measurable lesions, and pleural effusion and ascites disappeared in 2 of 7 patients (29%) and in 3 of 21 patients (14%), respectively. Median survival time was 151 days from the commencement of this treatment, with a median follow-up period of 260 days. Grade 3 or 4 leukopenia and neutropenia were observed in 11 (29%) and 12 (32%) patients, respectively. Seven patients (18%) died within 30 days of the last administration of paclitaxel.ConclusionWeekly paclitaxel seems to be active as second-line chemotherapy against metastatic and recurrent gastric cancer. Further study is needed to confirm the efficacy and safety of weekly paclitaxel.

Proton Beam Therapy for Unresectable Malignancies of the Nasal Cavity and Paranasal Sinuses

PURPOSE The cure rate for unresectable malignancies of the nasal cavity and paranasal sinuses is low. Because irradiation with proton beams, which are characterized by their rapid fall-off at the distal end of the Bragg peak and sharp lateral penumbra, depending on energy, depth, and delivery, provide better dose distribution than X-ray irradiation, proton beam therapy (PBT) might improve treatment outcomes for conditions located in proximity to risk organs. We retrospectively analyzed the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses. METHODS AND MATERIALS We reviewed 39 patients in our database fulfilling the following criteria: unresectable malignant tumors of the nasal cavity, paranasal sinuses or skull base; N0M0 disease; and treatment with PBT (>60 GyE) from January 1999 to December 2006. RESULTS Median patient age was 57 years (range, 22-84 years); 22 of the patients were men and 17 were women. The most frequent primary site was the nasal cavity (n=26, 67%). The local control rates at 6 months and 1 year were 84.6% and 77.0%, respectively. With a median active follow-up of 45.4 months, 3-year progression-free and overall survival were 49.1% and 59.3%, respectively. The most common acute toxicities were mild dermatitis (Grade 2, 33.3%), but no severe toxicity was observed (Grade 3 or greater, 0%). Five patients (12.8%) experienced Grade 3 to 5 late toxicities, and one treatment-related death was reported, caused by cerebrospinal fluid leakage Grade 5 (2.6%). CONCLUSION These findings suggest that the clinical profile of PBT for unresectable malignancies of the nasal cavity and paranasal sinuses make it is a promising treatment option.

Proton Beam Therapy as a Nonsurgical Approach to Mucosal Melanoma of the Head and Neck: A Pilot Study

PURPOSE The aim of this pilot study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the head and neck. METHODS AND MATERIALS Patients with mucosal melanoma of the head and neck with histologically confirmed malignant melanoma and N0 and M0 disease were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 Gy equivalents (GyE) in 15 fractions. RESULTS Fourteen consecutive patients were enrolled from January 2004 through February 2008. Patient characteristics were as follows: median age 73 years old (range, 56 to 79 years); male/female ratio, 7/7; and T stage 1/2/3/4, 3/2/0/9. All patients were able to receive the full dose of proton therapy. The most common acute toxicities were mucositis (grade 3, 21%) and mild dermatitis (grade 3, 0%). As for late toxicity, 2 patients had a unilateral decrease in visual acuity, although blindness did not occur. No treatment-related deaths occurred throughout the study. Initial local control rate was 85.7%, and, with a median follow-up period of 36.7 months, median progression-free survival was 25.1 months, and 3-year overall survival rates were 58.0%. The most frequent site of first failure was cervical lymph nodes (6 patients), followed by local failure in 1 patient and lung metastases in 1 patient. On follow-up, 5 patients died of disease, 4 died due to cachexia caused by distant metastases, and 1 patient by carotid artery perforation cause by lymph nodes metastases. CONCLUSIONS Proton beam radiotherapy showed promising local control benefits and would benefit from ongoing clinical study.

Phase II Study of Cetuximab Plus Concomitant Boost Radiotherapy in Japanese Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Background We investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck. Methods Patients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab (400 mg/m2 initial dose then 250 mg/m2 weekly) for 7 weeks plus concomitant boost radiotherapy (weeks 2–7: once daily [1.8 Gy] for 3.6 weeks, then twice daily [1.8 Gy morning and 1.5 Gy afternoon] for 2.4 weeks). The primary endpoint was treatment completion rate (the rate of treated patients completing ≥70% of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule). Results Twenty-two patients were evaluable. The treatment completion rate was 100% (95% confidence interval 85–100). The response rate 8 weeks post-radiotherapy was 82% (95% confidence interval 60–95). The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation (73%); dermatitis (27%); and infection, radiation skin injury and stomatitis (23% each). Conclusions Cetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck.

Analysis of dose-volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer

PURPOSE To evaluate dose-volume histogram (DVH) parameters as predictors of radiation pneumonitis (RP) in esophageal cancer patients treated with definitive concurrent chemoradiotherapy. PATIENTS AND METHODS Thirty-seven esophageal cancer patients treated with radiotherapy with concomitant chemotherapy consisting of 5-fluorouracil and cisplatin were reviewed. Radiotherapy was delivered at 2 Gy per fraction to a total of 60 Gy. For most of the patients, two weeks of interruption was scheduled after 30 Gy. The percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively), and the mean lung dose (MLD) were analyzed. RESULTS Ten (27%) patients developed RP of grade 2; 2 (5%), grade 3; 0 (0%), grade 4; and 1 (3%), grade 5. By univariate analysis, all DVH parameters (i.e., V5-V50 and MLD) were significantly associated with grade 2 RP (p < 0.01). The incidences of grade 2 RP were 13%, 33%, and 78% in patients with V20s of 24%, 25-36%, and 37%, respectively. The optimal V20 threshold to predict symptomatic RP was 30.5% according to the receiver operating characteristics curve analysis. CONCLUSION DVH parameters were predictors of symptomatic RP and should be considered in the evaluation of treatment planning for esophageal cancer.

Dose–Volume Histogram Analysis of the Safety of Proton Beam Therapy for Unresectable Hepatocellular Carcinoma

PURPOSE To evaluate the safety and efficacy of radiotherapy using proton beam (PRT) for unresectable hepatocellular carcinoma. METHODS AND MATERIALS Sixty consecutive patients who underwent PRT between May 1999 and July 2007 were analyzed. There were 42 males and 18 females, with a median age of 70 years (48-92 years). All but 1 patient had a single lesion with a median diameter of 45 mm (20-100 mm). Total PRT dose/fractionation was 76-cobalt Gray equivalent (CGE)/20 fractions in 46 patients, 65 CGE/26 fractions in 11 patients, and 60 CGE/10 fractions in 3 patients. The risk of developing proton-induced hepatic insufficiency (PHI) was estimated using dose-volume histograms and an indocyanine-green retention rate at 15 minutes (ICG R15). RESULTS None of the 20 patients with ICG R15 of less than 20% developed PHI, whereas 6 of 8 patients with ICG R15 values of 50% or higher developed PHI. Among 32 patients whose ICG R15 ranged from 20% to 49.9%, PHI was observed only in patients who had received 30 CGE (V30) to more than 25% of the noncancerous parts of the liver (n = 5) Local progression-free and overall survival rates at 3 years were 90% (95% confidence interval [CI], 80-99%) and 56% (95% CI, 43-69%), respectively. A gastrointestinal toxicity of Grade ≥2 was observed in 3 patients. CONCLUSIONS ICG R15 and V30 are recommended as useful predictors for the risk of developing PHI, which should be incorporated into multidisciplinary treatment plans for patients with this disease.

Multicenter phase II study of an opioid-based pain control program for head and neck cancer patients receiving chemoradiotherapy

BACKGROUND The aim of this multi-center phase II study was to clarify the clinical benefit of an opioid-based pain control program for head and neck cancer patients during chemoradiotherapy. PATIENTS AND METHODS Head and neck cancer patients who were to receive definitive or postoperative chemoradiotherapy were enrolled. The opioid-based pain control program consisted of a three-step ladder, with basic regimens of: The primary endpoint of this study was compliance with radiotherapy. RESULTS A total of 101 patients from 10 institutions were registered between February 2008 and May 2009 and included in the analysis. The major combination chemotherapy regimen was cisplatin alone (76%). The rate of completion of radiotherapy was 99% and the rate of unplanned breaks in radiotherapy was 13% (13/101, 90% confidence interval: 9.9-16.5%). Median maximum quantity of morphine used per day was 35 mg (range 0-150 mg). CONCLUSIONS Use of a systematic pain control program may improve compliance with CRT.

Induction Chemotherapy with Docetaxel, Cisplatin and S-1 Followed by Proton Beam Therapy Concurrent with Cisplatin in Patients with T4b Nasal and Sinonasal Malignancies

OBJECTIVE For the treatment of patients with T4b nasal and sinonasal malignancies, definitive chemoradiotherapy was contraindicated due to the risk of brain damage and blindness. However, combination chemotherapy with docetaxel, cisplatin and S-1 is well tolerated and effective. We conducted a retrospective analysis to evaluate the efficacy and feasibility of induction chemotherapy using docetaxel, cisplatin and S-1 followed by proton beam therapy concurrent with cisplatin. METHODS Thirteen patients treated with docetaxel, cisplatin and S-1 were analyzed. Docetaxel, cisplatin and S-1 consisted of 60-70 mg/m(2)/day docetaxel on day 1, 70 mg/m(2)/day cisplatin on day 1 and 60-80 mg/m(2)/day S-1 on days 1-14. Treatment was repeated every 3-4 weeks with a maximum number of three treatment cycles. According to the response to docetaxel, cisplatin and S-1, patients received either proton beam therapy concurrent with 20 mg/m(2)/day cisplatin on days 1-4 every 3 weeks or proton beam therapy alone. RESULTS Neutropenia represented the most common Grade 3/4 hematological toxicity (76.9%), while the most frequently observed non-hematological toxicity was nausea (23.0%). After the completion of docetaxel, cisplatin and S-1, the overall response rate was 38.4% (5 of 13), with 1 patient achieving complete response and 4 patients achieving partial response. Subsequently, 10 patients received proton beam therapy concurrent with cisplatin, 2 received proton beam therapy alone and 1 received palliative radiation. No severe toxicity was observed during proton beam therapy. After the completion of proton beam therapy, 11 patients (84.6%) achieved complete response and no brain damage or blindness occurred. CONCLUSIONS Induction chemotherapy with docetaxel, cisplatin and S-1 followed by proton beam therapy concurrent with cisplatin is well tolerated and displays promising antitumor activity that warrants further investigation.

Phase II study of proton beam therapy as a nonsurgical approach for mucosal melanoma of the nasal cavity or para-nasal sinuses.

PURPOSE The aim of this phase II study was to assess the clinical benefit of proton beam therapy for mucosal melanoma of the nasal cavity and para-nasal sinuses. MATERIALS AND METHODS N0M0 mucosal melanoma of the nasal cavity and para-nasal sinuses were enrolled. Proton therapy was delivered three times per week with a planned total dose of 60 GyE in 15 fractions. Primary endpoint was local control rate at 1 year after treatment. Based on the results of a pilot study, the local control rate was estimated at 75%. RESULTS Thirty-two patients were enrolled from June 2008 through October 2012. Patient characteristics were as follows: median age 73 years (range, 36-89 years); male/female ratio, 12/20; and T stage 3/4, 11/21. Local control rate at 1 year was 75.8% (95% CI: 63.8-92.4%). With a median follow-up period of 36.4 months, 3-year overall survival rate was 46.1%. The most frequent pattern of first failure was distant metastasis. The main cause of death was cancer death due to distant metastases (93.3%). CONCLUSIONS Proton beam therapy showed sufficient local control benefits for mucosal melanoma as an alternative treatment of surgery.

The Effectiveness of Chemoradiation Therapy and Salvage Surgery for Hypopharyngeal Squamous Cell Carcinoma

OBJECTIVE The objective of this study was to evaluate the results of salvage surgery after definitive chemoradiation for hypopharyngeal squamous cell carcinoma. METHODS This was a retrospective cohort study. Of the 79 patients with previously untreated hypopharyngeal squamous cell carcinoma who received definitive chemoradiation from January 2004 to January 2009, 24 who had recurrence and underwent salvage surgery at the National Cancer Center Hospital East, Chiba, Japan, were enrolled in this study. RESULTS Of the 24 patients who underwent salvage surgery with curative intent, 13 had an isolated local failure, eight had an isolated neck failure and three had combined local and regional failure. Postoperative surgical complications were observed in eight (33.3%) patients. Of the 24 patients undergoing salvage surgery, 12 (50%) had recurrence. In 11 of these patients, death ensued from salvage failure, defined as the presence of any recurrence after salvage treatment. The causes of cancer-specific death ensuing from salvage failure were regional recurrence of the tumor (n = 6) (one of whom had concurrent distant metastases) and distant metastases alone (n = 5). No local recurrence after salvage surgery was observed in our group of patients. The disease-free and overall 24-month survival rates were 49.0 and 50.0%, respectively. Those patients who initially presented with unresectable disease had lower overall survival compared with those who initially presented with resectable disease (P = 0.0003). CONCLUSIONS The oncologic outcomes were acceptable in those patients in whom salvage surgery was carried out. Those who initially presented with unresectable disease had a poor prognosis.