ABSTRACT
Background. Anxiety/depressive symptoms are common in patients with chronic fatigue syndrome- (CFS-) like illness. Qigong as a modality of complementary and alternative therapy has been increasingly applied by patients with chronic illnesses, but little is known about the effect of Qigong on anxiety/depressive symptoms of the patients with CFS-like illness. Purpose. To investigate the effects of Qigong on fatigue, anxiety, and depressive symptoms in patients with CFS-illness. Methods. One hundred and thirty-seven participants who met the diagnostic criteria for CFS-like illness were randomly assigned to either an intervention group or a waitlist control group. Participants in the intervention group received 10 sessions of Qigong training twice a week for 5 consecutive weeks, followed by home-based practice for 12 weeks. Fatigue, anxiety, and depressive symptoms were assessed at baseline and postintervention. Results. Total fatigue score [F(1,135) = 13.888, P < 0.001], physical fatigue score [F(1,135) = 20.852, P < 0.001] and depression score [F(1,135) = 9.918, P = 0.002] were significantly improved and mental fatigue score [F(1,135) = 3.902, P = 0.050] was marginally significantly improved in the Qigong group compared to controls. The anxiety score was not significantly improved in the Qigong group. Conclusion. Qigong may not only reduce the fatigue symptoms, but also has antidepressive effect for patients with CFS-like illness. Trial registration HKCTR-1200.
ABSTRACT
BACKGROUND: Chronic fatigue is common in the general population. Complementary therapies are often used by patients with chronic fatigue or chronic fatigue syndrome to manage their symptoms. PURPOSE: This study aimed to assess the effect of a 4-month qigong intervention program among patients with chronic fatigue or chronic fatigue syndrome. METHODS: Sixty-four participants were randomly assigned to either an intervention group or a wait list control group. Outcome measures included fatigue symptoms, physical functioning, mental functioning, and telomerase activity. RESULTS: Fatigue symptoms and mental functioning were significantly improved in the qigong group compared to controls. Telomerase activity increased in the qigong group from 0.102 to 0.178 arbitrary units (p < 0.05). The change was statistically significant when compared to the control group (p < 0.05). CONCLUSION: Qigong exercise may be used as an alternative and complementary therapy or rehabilitative program for chronic fatigue and chronic fatigue syndrome.
Subject(s)
Activities of Daily Living , Breathing Exercises , Fatigue Syndrome, Chronic/therapy , Fatigue/therapy , Telomerase/metabolism , Adult , Fatigue/blood , Fatigue Syndrome, Chronic/blood , Female , Humans , Male , Middle Aged , Treatment Outcome , Waiting ListsABSTRACT
PURPOSE: To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: All patients were irradiated with the same RT technique to > or =66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil). RESULTS: Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p > or = 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05). CONCLUSIONS: Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Carcinoma/radiotherapy , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Adult , Aged , Carcinoma/pathology , Cisplatin/administration & dosage , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Dose Fractionation, Radiation , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Multivariate Analysis , Nasopharyngeal Neoplasms/pathology , Neoplasm Staging , Treatment OutcomeABSTRACT
This study aimed to investigate the psychophysiological outcomes of different psychosocial interventions for breast cancer patients. Participants were randomly assigned into 3 intervention groups, namely, Body-Mind-Spirit (BMS), Supportive-Expressive (SE), and Social Support Self-Help (SS) groups; a no-intervention group was used as control. Salivary cortisol was used as the physiological stress marker. Distress level, mental adjustment, emotional control, and social support were measured. Data were collected at baseline, 4 month, and 8 month. Preliminary results indicated that BMS intervention produced the greatest and the most sustained effects. It enhanced positive social support, reduced psychological distress, emotional control, and negative mental adjustment. Total salivary cortisol was lowered after 8 months. Most participants in SE groups indicated the treatment helpful, but changes in psychophysiological outcomes were not statistically significant. Participants in SS groups seemed less likely to benefit from the intervention. The no intervention control group indicated a reduction in social support. These outcomes suggest that active professional intervention is more likely to yield therapeutic effects. In particular, psychosocial intervention attending to the spiritual dimension contributes to positive outcomes.
Subject(s)
Asian People/ethnology , Asian People/psychology , Breast Neoplasms/psychology , Breast Neoplasms/therapy , Hydrocortisone/blood , Mind-Body Therapies , Self-Help Groups , Social Support , Adaptation, Psychological/physiology , Adult , Breast Neoplasms/physiopathology , Cancer Care Facilities , Cross-Cultural Comparison , Cultural Characteristics , Feasibility Studies , Female , Follow-Up Studies , Hong Kong , Humans , Medicine, Chinese Traditional , Middle Aged , Pilot Projects , Psychology, Clinical , Psychophysiology , Social WorkABSTRACT
PURPOSE: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). RESULTS: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. CONCLUSIONS: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.
Subject(s)
Carcinoma/radiotherapy , Nasopharyngeal Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/pathology , Cisplatin/administration & dosage , Combined Modality Therapy , Dose Fractionation, Radiation , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/pathology , Neoplasm Staging , Radiation Injuries/complications , Stomatitis/etiology , Survival AnalysisABSTRACT
OBJECTIVE: To evaluate the efficacy and toxicity of concomitant chemo-radiotherapy (CCRT) followed by adjuvant chemotherapy (ACT) in Chinese patients with locoregionally advanced nasopharygeal carcinoma (NPC). METHODS: Seventy-four patients with stage III and IV (UICC1997) were treated by Intergroup 0099 regimen, consisting of CCRT using cisplatin 100 mg/m(2) on D1, 22, and 43 of radiotherapy, followed by ACT using cisplatin 80 mg x m(-2) x d(-1) and 5-Fu 1 g x m(-2) x 4 d(-1) given from D71, 99, and 127. All the patients were irradiated with conventional fractionation to a total dose of 68 Gy to the nasopharynx and 66 Gy to the neck. Acute toxicity and late complication were assessed by the RTOG radiation morbidity scoring scheme. RESULTS: With a median follow-up of 49 months, the overall 5-year survival and relapse-free survival rates were 71.3% and 43.5% respectively. No grade 5 toxicity was observed in this series, the main grade 3/4 acute toxicity events were hematologic toxicity in 25 patients (33.8%), mucositis in 19 patients (25.7%), and grade 3 skin disease in 6 (8.1%), respectively. The compliance rates were 100.0% for radiotherapy, 75.7% for CCRT, and 47.3% for CCRT plus ACT. The main grade 3/4 late complications were severe salivary gland toxicity (17 cases), ear injury (13 cases), and the neck skin/subcutaneous tissue disease (7 cases). The 5-year cumulative incidence of late toxicity was 44.3%. CONCLUSION: Compared with routine radiotherapy, the concomitant chemo-radiotherapy may improve the outcome of locoregionally advanced NPC in the Chinese patients, with higher incidence of severe acute toxicities and similar late complications.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/pathology , Neoplasm Staging , Radiotherapy/adverse effects , Treatment OutcomeABSTRACT
Hepatocellular carcinoma is an important health problem in Asia. A blend of herbal extracts containing radix bupleuri (KY88) was tested for its effects on liver cancer cells. A hepatocellular carcinoma cell line (HB8064) was cultured with methanol extract of KY88. We were able to produce a dose-dependent inhibition of cancer cell proliferation. At IC50 and IC100, KY88 induces a DNA ladder pattern, indicating the presence of apoptosis. We also checked the changes of the levels of interleukin (IL)-2, -4 and -6, interferon (INF)-gamma and tumor necrosis factor (TNF)-alpha by ELISA kits. After 24 hours of culture, there was activation of IL-2 and -4 and TNF-alpha. However, significant changes were observed only for IL-4 and TNF-alpha. Therefore, we concluded that KY88 is able to induce apoptosis, which may be regulated through changes in IL-4 and TNF-alpha.
Subject(s)
Apoptosis/drug effects , Carcinoma, Hepatocellular/pathology , Drugs, Chinese Herbal/pharmacology , Liver Neoplasms/pathology , Enzyme-Linked Immunosorbent Assay , Humans , Interleukin-4/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesisABSTRACT
PURPOSE: To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Patients with Ho's stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B. RESULTS: Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009). CONCLUSION: An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Carcinoma/radiotherapy , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Administration, Oral , Adult , Aged , Bleomycin/administration & dosage , Carcinoma/pathology , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Combined Modality Therapy , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Male , Methotrexate/administration & dosage , Middle Aged , Nasopharyngeal Neoplasms/pathology , Neoplasm Metastasis , Tegafur/administration & dosage , Treatment Outcome , Uracil/administration & dosage , Vincristine/administration & dosageABSTRACT
BACKGROUND: To evaluate the toxicity and efficacy of concurrent chemoirradiation with cisplatin followed by adjuvant ifosfamide, 5-fluorouracil and leucovorin in patients with stage IVb nasopharyngeal carcinoma (NPC) PATIENTS AND METHODS: Between October 1998 and August 2001, 35 Chinese patients with stage IVb NPC (N3a:12, N3b:23) were treated with by concurrent chemoirradiation using cisplatin 100 mg/m2 on days 1, 22, and 43 of radiotherapy, followed by adjuvant chemotherapy with 1.4 g/m2, ifosfamide, 450 mg/m2 5-fluorouracil, and 20 mg/m2 leucovorin daily for 5 days and repeated every 3 weeks for three cycles. Radiotherapy was given using standard fractionation at 2 Gy/day to a total of 68 Gy to the nasopharynx and 66 Gy to the neck. RESULTS: All patients completed the prescribed radiotherapy. Twenty-three patients (66%) completed all scheduled cycles of chemotherapy. The compliance rate for concurrent and adjuvant chemotherapy was 71% and 80%, respectively. Grade 3 mucositis occurred in 37%, and grade 3 dermatitis occurred in 11.5% during radiotherapy. Grade 3 neutropenia occurred in 17% during concurrent chemotherapy, and grade 3-4 neutropenia occurred in 48.5% during adjuvant chemotherapy. There were no treatment-related deaths. With a median follow-up of 31 months, the 3-year relapse-free rate was 60%, and the 3-year overall survival rate was 74%. Locoregional control was excellent, with a 3-year local and nodal relapse-free rate of 91% and 83%, respectively. Eleven patients (31%) had developed distant metastases, and the 3-year distant metastasis-free rate was 66%. CONCLUSIONS: The chemotherapy regimen tested is practical with an acceptable compliance rate. Despite having a more advanced stage disease, the observed outcome of our patients seems to be comparable with other series using platinum-based adjuvant chemotherapy. Further investigation to confirm the benefit of using the study regimen in advanced stage NPC is warranted.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma/drug therapy , Carcinoma/radiotherapy , Ifosfamide/administration & dosage , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Adult , Aged , Carcinoma/mortality , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Combined Modality Therapy , Dermatitis/etiology , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Ifosfamide/adverse effects , Leucovorin/administration & dosage , Leucovorin/adverse effects , Leukopenia/etiology , Male , Middle Aged , Nasopharyngeal Neoplasms/mortality , Survival Rate , Vomiting/etiologyABSTRACT
The use of herbal medicine is a common practice among Chinese women with breast cancer. Yunzhi (Voriolus versicolor), a substance that is regarded as a biological response modifier, is frequently used. The aim of the present study is to evaluate the anti-proliferative action of, Yunzhi, polysaccharide peptide (PSP), on breast cancer cells. Breast cancer cells (MDA-MB-231) were cultured with and without PSP for 7 days. Cell growth at 24, 72, 120 and 168 hours was measured by Cell Proliferation Reagent (WST-1). Cells treated with PSP were found to have a significant reduction in cell proliferation as compared to controls after 72 hours of incubation. This lasted for 168 hours. When the effect of PSP on apoptosis was studied by the TdT-mediated X-dUTP nick end-labeling (TUNEL) assay, we found that PSP had a significant effect upon apoptosis from 24 hours onward. Immunostaining showed that PSP increased p21 expression and decreased cyclin D1 expression. In conclusion, PSP is effective in inhibiting cell proliferation through apoptosis. The mechanism for the apoptosis may be through up-regulation of p21 and down-regulation of cyclin D1.
Subject(s)
Apoptosis/drug effects , Cyclin D1/drug effects , Down-Regulation , Gene Expression Regulation, Neoplastic/drug effects , Proteoglycans/pharmacology , Up-Regulation , Breast Neoplasms/drug therapy , Cyclin D1/genetics , Female , Humans , In Situ Nick-End Labeling , Time Factors , Tumor Cells, Cultured/drug effectsABSTRACT
PURPOSE: To evaluate the efficacy and complication of linear accelerator-based stereotactic radiosurgery (SRS) when used as salvage treatment for early-stage persistent and recurrent nasopharyngeal carcinoma (NPC) after primary radiotherapy (RT). MATERIALS AND METHODS: Between March 1998 and June 2001, 18 patients (15 men and 3 women; median age 46 years, range 32-84) with locally persistent or recurrent NPC confined to the nasopharynx (rT1) or with limited extension to the nasal fossa or parapharyngeal space (rT2) were treated by SRS. Thirteen patients had rT1 disease and 5 had rT2 disease. Most patients had disease not amenable to surgery or brachytherapy. All patients had undergone previous radical RT. Persistent disease was defined as tumor relapse within 4 months of completion of primary RT, and recurrence as tumor relapse beyond 4 months. Seven patients were treated for persistent disease, eight for a first recurrence, and three for a second recurrence. SRS was performed using multiple noncoplanar arcs of photons delivered to the target volume, which was defined by axial CT at a 3 mm thickness, supplemented by MRI in selected patients (67%). The median target volume was 5.3 cm(3) (range 2.2-16.9). The median SRS dose was 12.5 Gy (range 11-14) delivered to the 80% isodose line. All patients underwent serial nasopharyngoscopy and imaging after SRS. The median follow-up was 26 months (range 11-48). RESULTS: After SRS, 16 (89%) of 18 patients had complete regression of tumor as assessed by nasopharyngoscopy and biopsy. Four patients with an initial complete response to SRS subsequently developed local relapse again, with one recurrence developing outside the target volume 8 months after SRS and three within the target volume at 6-26 months after SRS. Two patients with local disease controlled by SRS developed relapse in other sites (neck node and liver metastases). The actuarial 2-year local control rate after SRS was 72%. Patients treated for persistent disease had a better local control rate (100%; 7 of 7) than those treated for recurrent disease (46%; 5 of 11). Patients with rT1 disease also had a better outcome after SRS compared with those with rT2 disease, with a control rate of 77% (10 of 13) for rT1 disease and 40% (2 of 5) for rT2 disease. Treatments were well tolerated, with no acute side effects. One patient had radiologic evidence of temporal lobe necrosis, although the right temporal lobe had already received a high dose during prior RT. That patient also developed additional local recurrence and liver metastases and died. The actuarial 2-year survival rate was 86%. CONCLUSIONS: Our preliminary results indicate that SRS is an effective treatment modality for persistent and recurrent early-stage NPC, with early control rates comparable to other salvage treatments such as brachytherapy and nasopharyngectomy. A modest SRS dose at 12.5 Gy also appears to be effective and is associated with minimal morbidities. More clinical experience and longer follow-up are needed to validate our results and to address fully the role of SRS in salvaging local failures of NPC.
Subject(s)
Carcinoma/surgery , Nasopharyngeal Neoplasms/surgery , Radiosurgery , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Carcinoma/mortality , Carcinoma/pathology , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Life Tables , Magnetic Resonance Imaging , Male , Middle Aged , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Neoplasm Recurrence, Local , Organoplatinum Compounds/administration & dosage , Particle Accelerators , Postoperative Complications/etiology , Radiation Injuries/etiology , Radiosurgery/adverse effects , Salvage Therapy , Survival Analysis , Survival Rate , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
To evaluate the efficacy and toxicity of capecitabine as a salvage chemotherapy regimen in Chinese patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy, 17 patients with recurrent or metastatic NPC previously treated with platinum-based chemotherapy as adjuvant or palliative treatments received oral capecitabine at a dose of 1.25 G/m(2) twice daily in 3-week cycles consisting of 2 weeks of treatment followed by rest period of 1 week. Seven patients had local recurrence, seven had distant metastases, one had loco-regional recurrence, and two had both local/regional recurrence and distant metastases. Patients received a median number of three cycles of capecitabine (range: 1-6). The median follow-up was 7.5 months (range: 3-25.3). All patients were included in the efficacy and adverse events analysis. Three patients (17.6%) achieved partial response and one patient (5.9%) achieved complete response, with an overall response rate of 23.5% (95% confidence interval, 7-50%). The duration of response's were 4.2, 5, 6+, and 23.1+ months. Nine patients (52.9%) had stable disease whereas four (23.5%) had progressive disease. The median time to progression was 4.9 months. The median survival was 7.6 months. Five patients are still alive with an estimated 1-year survival rate of 35%. Treatment-related adverse events were generally mild except hand-foot syndrome which occurred in 58.8% of patients. Capecitabine is an effective salvage regimen in patients with recurrent and metastatic NPC. Capecitabine as a single agent or in combination with other chemotherapeutic agents or treatment modalities should be further studied in NPC.
Subject(s)
Antineoplastic Agents/therapeutic use , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Nasopharyngeal Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Antineoplastic Agents/adverse effects , Capecitabine , Cisplatin/therapeutic use , Deoxycytidine/adverse effects , Disease Progression , Drug Administration Schedule , Female , Fluorouracil/analogs & derivatives , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Nasopharyngeal Neoplasms/mortality , Neoplasm Recurrence, Local/mortality , Salvage Therapy/methods , Survival RateABSTRACT
The use of cisplatin as a potential radiosensitizer in nasopharyngeal carcinoma (NPC) has produced encouraging results in clinical trials. In order to provide information on improving the design of clinical treatments, we investigated the effect of cisplatin dose, and the time interval and sequence between administration of cisplatin and radiation on cell survival of two NPC cell lines, CNE1 and SUNE1. When cisplatin was applied first, an exposure time of 24 h resulted in up to 2.6-fold increase in cell death and 7-fold increase in radiation effect (cell survival after cisplatin/cell survival after cisplatin plus radiation) in the cisplatin-radiation combination treatment compared to the cells treated with cisplatin for 4 h. When radiation was applied first, a shorter interval time of 4 h followed by cisplatin treatment resulted in up to 3-fold increase in cell death and a 3-fold enhanced radiation effect over longer time intervals of 24 h. By changing the order of radiation and cisplatin treatment alone, a 2-fold difference in radiation effect was observed. The differential cytotoxicity was partially explained by the alterations in cell cycle distribution. Our results indicate the importance of scheduling the radiation and cisplatin combination regimens on the survival of NPC cells.
Subject(s)
Cisplatin/therapeutic use , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/radiotherapy , Radiation-Sensitizing Agents/administration & dosage , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Survival/drug effects , Cell Survival/radiation effects , Cisplatin/administration & dosage , Combined Modality Therapy , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Drug Administration Schedule , Drug Evaluation, Preclinical , Humans , Nasopharyngeal Neoplasms/pathology , Tumor Cells, Cultured , Tumor Stem Cell AssayABSTRACT
PURPOSE: To evaluate the toxicity and efficacy of concomitant chemoirradiation (CRT) followed by adjuvant chemotherapy compared with radiotherapy (RT) alone in Chinese patients with locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: Between March 1997 and September 2000, 47 Chinese patients with Stage III (n = 9, 19%) and IV (n = 38, 81%) NPC were treated with by CRT using cisplatin 100 mg/m(2) on Days 1, 22, and 43 of RT, plus adjuvant chemotherapy using cisplatin 80 mg/m(2) for 1 day and 5-fluorouracil 1 g/m(2) for 4 days on Days 71, 99, and 127. These patients were then compared with a cohort of 47 patients treated between 1990 and 1993 with RT alone, who were matched with respect to T stage, N stage, nodal bilaterality, nodal level, and nodal size. The RT techniques were similar in the two groups but different dose and fractionation schemes were used. The median biologic equivalent dose to 2 Gy per fraction delivered to the nasopharynx was 68 Gy in the CRT group and 65.3 Gy in the RT-alone group. RESULTS: The compliance rates were 62% for concomitant chemotherapy and 40% for adjuvant chemotherapy. No treatment-related deaths occurred. At the end of treatment, 96% of the CRT group and 79% of the RT-alone group achieved a complete response (p = 0.013). With a median follow-up of 26 months, the 3-year relapse-free survival, disease-specific survival, overall survival, local relapse-free survival, nodal relapse-free survival, and distant metastasis-free survival rate for the CRT group and the RT-alone group was 62% vs. 44% (p = 0.048), 67% vs. 71% (p = 0.88), 65% vs. 69% (p = 0.93), 87% vs. 75% (p = 0.059), 95% vs. 80% (p = 0.026), and 75% vs. 70% (p = 0.84), respectively. CONCLUSION: Our experience indicates that concomitant CRT improves locoregional control in Chinese patients with locoregionally advanced NPC, but our analyses failed to detect any impact on distant failure and survival. The failure to reduce distant metastasis and improve survival may have related in part to the more advanced disease stage in our patients and the relatively low compliance rate of adjuvant chemotherapy. Our findings suggest caution should be exercised in extrapolating the findings of the Intergroup Study 0099 to Chinese patients, and confirmatory results from prospective randomized studies in the endemic population are needed.