Yuen-Liang Lai

A phase III study of adjuvant chemotherapy in advanced nasopharyngeal carcinoma patients

PURPOSE To evaluate the role of adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma (NPC) patients, we conducted a randomized Phase III trial comparing radiotherapy (RT) followed by adjuvant chemotherapy to RT alone in patients with advanced NPC. METHODS AND MATERIALS Between November 1994 and March 1999, 157 patients with Stage IV, M(0) (UICC/AJCC, 1992) advanced NPC disease were randomized to receive standard radiotherapy, as follows: 35-40 fractions, 1.8-2.0 Gy/fraction/day, 5 days/week, to a total dose 70-72 Gy with or without 9 weekly cycles of 24-h infusional chemotherapy (20 mg/m(2) cisplatin, 2,200 mg/m(2) 5-fluorouracil, and 120 mg/m(2) leucovorin) after RT. Of 157 patients enrolled, 154 (77 radiotherapy, 77 combined therapy) were evaluable for survival and toxicity analysis. RESULTS With a median follow-up of 49.5 months, the 5-year overall survival and relapse-free survival rates were 60.5% vs. 54.5% (p = 0.5) and 49.5% vs. 54.4% (p = 0.38) for the radiotherapy-alone group and the combined radiotherapy and adjuvant chemotherapy group, respectively. The Cox regression showed that the hazard rates ratio of combined treatment to RT alone was 0.673 (p value = 0.232); the 95% confidence interval was 0.352 and 1.288, respectively. Patients who received combined treatment had a lower systemic relapse rate than radiotherapy-alone patients, according to relapse pattern analysis. The incidence of leukopenia (>or= Grade 3) occurred in 17 out of 819 (2.1%) cycles of weekly chemotherapy. No patient developed moderate to severe mucositis (>or= Grade 3). CONCLUSIONS We conclude that adjuvant chemotherapy after RT for patients with advanced NPC has no benefit for overall survival or relapse-free survival.

Prevalence, Detection and Treatment of Delirium in Terminal Cancer Inpatients: A Prospective Survey

BACKGROUND Delirium is a common syndrome in terminal cancer patients. However, its detection and treatment by palliative care teams are not well documented. This survey aimed to determine the prevalence, detection and treatment of delirium in terminal cancer inpatients. METHODS The survey was conducted in Mackay Hospice and Palliative Care Center, Taiwan, from August 2006 to January 2007. All terminal cancer inpatients were invited to participate. The Delirium Rating Scale-Chinese Version was used by a research assistant as the screening instrument. Patients detected by screening were reviewed by psychiatrists to verify the diagnosis and determine the sub-type of delirium. The palliative care team members were asked to evaluate all the participants weekly. The medications used for delirium were obtained by a medical chart review. Result Two hundred and twenty eight participants (49.9%) among 457 inpatients were screened. The prevalence of delirium was 46.9% (n = 107). Of these, the most common subtype was hypoactive (68.2%, 95% confidence interval (CI): 59.4-77.0%). The mortality rate of inpatients with delirium (77.6%, 95% CI: 69.7-85.5%) was higher (P < 0.0001) than those without delirium (50.9%, 95% CI: 44.4-57.4%). The overall detection rate by any member of the palliative team was 44.9% (n = 48) (95% CI: 35.5-54.3%). The detection rate of the hypoactive subtype was only 20.5% (95% CI: 11.2-29.8%), which was significantly lower than that of the hyperactive/mixed subtypes (P < 0.0001). Therapy for delirium was prescribed in 42.1% (n = 45) (95% CI: 32.7-51.5%) with haloperidol being the most common medication. CONCLUSION The prevalence of delirium was high, but the rates of detection and treatment were low. Interventions are recommended to improve the diagnosis and treatment of delirium in palliative care units.

Radiotherapy for Postoperative Recurrent Uterine Cervical Carcinoma

From January 1980 to December 1985, a total of 110 patients with postoperative recurrent uterine cervical carcinoma were treated with radiotherapy. The mean age was 53 years. Ten patients were excluded due to incomplete treatment. The population was grouped according to the classification by Ciatto et al. into patients with central recurrence (n = 48), with peripheral limited recurrence (n = 43), and with peripheral massive recurrence (n = 9). The midpelvic dose given to patients with central recurrence was 40 to 45 Gy, followed by a boost given either by perineal teletherapy with 30 Gy or brachytherapy with 30 Gy at 0.5 cm. beneath the vaginal mucosa. For the peripheral group, the midpelvic dose was 50 Gy followed by a boost of 10 Gy through reduced portals. Further boost to the vaginal mucosa was given by either of the two methods mentioned above. The overall 5-year survival rate was 28%. In the group with central recurrence, it was 42% and in the group with peripheral recurrence 15%. Sixteen patients had persistent local tumor and 15 patients developed distant metastasis. Complications noted were proctitis (5%), cystitis (2%), vesicovaginal fistula (2%) and rectovaginal fistula (2%). Our data clearly indicate that radiotherapy was effective in controlling central recurrence, but for peripheral recurrence, control rate and prognosis were less favorable.

An open trial comparing haloperidol with olanzapine for the treatment of delirium in palliative and hospice center cancer patients

This study compared the efficacy between haloperidol and olanzapine to treat the delirious syndromes in the palliative and hospice center cancer patients. Patients those received hospice and palliative care, with an advanced cancer, and met the DSM-IV criteria for delirium were recruited. They were administered the DRS-c and CGI-S at the time point of T0, T1, T2, T3 during 1 week. 16 patients (M:F=9:7; mean age ± SD=61.13±16.5) in olanzapine group and 14 patients (M:F=4:10; mean age ± SD=68±12.14) in haloperidol group were recruited. In both groups there was significant difference in scores of DRS-c and CGI-S across time periods (haloperidol group: DRS-c: at T1, p=0.008; at T2, p=0.044; at T3, p=0.043 and CGI-S: at T1, p=0.012; olanzapine group: DRS-c: at T3, p=0.042 and CGIS: at T1, p=0.040). However, comparison of the scores of DRS-c and CGI-S across time periods between two groups showed no statistical difference. The results showed that the delirium improved in both groups but no statistic difference comparing both groups. Therefore, olanzapine might be a useful alternative to haloperidol in the treatment of delirium in advanced cancer patients.

A Good Ending-Holistic Care for Patients with Head and Neck Cancers

Terminal head and neck cancer is one of the most distressing ways a person may die as it affects the patients quality of life widely. The comprehensive multidisciplinary management of patients’ physical, psychosocial, and spiritual needs will enhance the possibility of patients and their families obtaining the best quality of life. This includes adequate symptom control, being treated as a whole person and achieving a sense of completion. By such holistic care, patients will experience a peaceful ending.

The Effect and Safety of Transdermal Fentanyl for Concurrent Chemoradiation Therapy-Induced Mucositis Pain in Head and Neck Cancer Patients

Purpose: This prospective, longitudinal study was to evaluate the efficacy and the safety of using TTS-fentanyl for severe oral mucositis pain induced by concurrent chemoradiotherapy (CCRT) in head and neck cancer (HNC) patients. Materials and Methods: Patients diagnosed as HNC and scheduled for concurrent chemoradiotherapy were eligible for this study. TTS-fentanyl was given with the initial dose of 25 μg/h when severe mucositis pain (numeric rating scale [NRS]≧7) occurred in spite of nonsteroid anti-inflammatory drugs (NSAID) and topical steroidal ointment use. The pain intensity was assessed every week and if severe pain persisted, another dose of 25 μg/h TTS-fentanyl was given. The adverse effects were recorded every week according to Common Toxicity Criteria (CTC) Version 2.0. Results: From October 2002 to March 2003, 21 male and 1 female receiving CCRT with HNC were recruited to this study. The mean NRS for pain significantly decreased from 7.65±0.99 (baseline) to 3.9±1.29 within the first week. In the fifth week, the NRS raised to 4.79±1.18 but was still lower than the baseline (p=0.003). The sufficient analgesia was achieved in 15 cases with a dose of 25 μg/h, in 5 cases with a dose of 50 μg/h, and in 1 case with a dose of 100 μg/h. One patient withdrew the TTS-fentanyl due to intolerable skin rash and vomiting in the second week. Besides, no one developed respiratory depression, mental clouding, or grade Ⅲ/IV gatrointestinal toxicities. Conclusion: TTS-fentanyl is effective and safe in the treatment of mucositis-induced pain which is resistant to NSAID in HNC patients receiving CCRT. TTS-fentanyl also spares the need to swallow pain killers in these patients suffering from odynophagia and/or dysphagia, as well as the time for titration of conventional analgesic drugs. Further larger series with randomized setting is warranted to evaluate the efficacy and safety of TTS-fentanyl for oral mucositis pain.

Concurrent Weekly Cisplatin and Radiotherapy Plus Adjuvant Chemotherapy for Nasopharyngeal Cancer –A Preliminary Study

Purpose : It has been shown that concurrent chemoradiotherapy (CCRT) confers significantly better survival in locally advanced nasopharyngeal carcinoma (NPC) compared with radiotherapy. We conducted a prospective pilot study to evaluate the efficacy and toxicity of a CCRT regimen using low-dose cisplatin (CDDP) for treatment of NPC to see if it enhanced radiation response and reduced chemotherapy-induced toxicity. Materials and Methods : A total of 14 patients were enrolled. The CCRT regimen consisted of radiotherapy (RT), 70~72 Gy to the primary tumor with concurrent CDDP 30 mg/m2 administered once a week for 7 to 8 weekly doses. After CCRT, 4 cycles of adjuvant CDDP, 20 mg/m2/day, and 5-FU, 1000 mg/m2 infused over 24 hours for 5 consecutive days were given monthly. Tumor response and toxicity were analyzed. Results : Eleven patients completed CCRT in 8 to 10 weeks, 3 patients delayed up to eleven weeks, and half (50%) received 4 complete courses of adjuvant chemotherapy. Ten (71.4%) patients had a complete response (CR) after CCRT, with an additional 3 achieving a CR after adjuvant chemotherapy, for a total of 13 (92.9%) out of 14. Adverse effects of CCRT included grade 3 or 4 oropharyngeal mucositis in 3 (21.4%) and grade 3 or 4 radiation dermatitis in 8 (57.1%). There was no severe renal or fatal toxicity from the treatment. At a median follow-up of 19.5 months, 1 patient still had residual tumor, 1 had recurrence and 2 had systemic metastases. Conclusion : CCRT followed by adjuvant chemotherapy was effective in a small series of NPC patients, with acceptable and reversible acute toxicity. This protocol deserves further investigation in randomized prospective trials.

Increase in Frequency of HPRT Mutation in Tongue Cancer Patients After Radiotherapy: Two Cases

The mutation frequency of the hypoxanthine-guanine phosphoribosyl transferase gene (HPRT ) in the peripheral T-lymphocytes of two patients treated with radiotherapy (RT) for tongue cancers was studied. The mutation or variant frequency (Vf) at the HPRT locus was assayed by an immunofluorescent staining method to monitor the genotoxic effects of RT. Both patients underwent conventional radical RT to a total tumor dose of 70 Gy, without chemotherapy (CT). The peripheral blood samples were obtained three times from each patientbefore RT (pre-RT), at a cumulative dose of 36-40 Gy (during RT), and immediately after the last irradiation (post-RT). The HPRT variant frequency did not change significantly during RT as compared to that of pre-RT, but increased significantly at post-RT. The Vf of HPRT in these tongue cancer patients post-RT exhibited a three-fold increase over that of pre-RT, implying a risk of genetic mutation for patients treated with RT.