Toxic epidermal necrolysis related to AP (pemetrexed plus cisplatin) and gefitinib combination therapy in a patient with metastatic non-small cell lung cancer.

Toxic epidermal necrolysis (TEN) is a rare acute life-threatening mucocutaneous disorder that is mostly drug-related (80%-95%). It is clinically characterized as a widespread sloughing of the skin and mucosa. AP regimen (pemetrexed plus cisplatin) has been the preferred first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). Gefitinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has already been recommended as a first-line treatment in EGFR-mutant metastatic NSCLC. We report rare presentation of TEN involving adverse effects of AP and gefitinib combination treatment in a 42-year-old woman diagnosed with metastatic NSCLC harboring an EGFR mutation. On the 21st day after administration of the first cycle of AP regimen and the 8th day after the initiation of gefitinib treatment, she developed an acne-like rash, oral ulcer, and conjunctivitis, which later became blisters and ultimately denuded. The characteristic clinical courses were decisive for the diagnosis of TEN. Treatment with systemic steroids and immunoglobulin as well as supportive treatment led to an improvement of her general condition and a remarkable recovery.

Treatment Patterns and Survival Outcomes of Non-Small Cell Lung Cancer Patients Initially Diagnosed With Brain Metastases in Real-World Clinical Practice.

BACKGROUND: This study aimed to comprehensively analyze the characteristics, treatment patterns, and survival outcomes of non-small-cell lung cancer (NSCLC) patients initially diagnosed with brain metastases (BMs) in real-world practice. METHODS: We enrolled NSCLC patients initially diagnosed with BMs between Jan 2004 and Jan 2018 in our institution. Patient demographics, treatment modalities, and survival outcomes were then analyzed. Brain localized treatment (BLT) included early brain radiotherapy (EBR), deferred brain radiotherapy (DBR), and surgery. RESULTS: A total of 954 patients were identified. Concerning initial treatment, 525 patients (55.0%) received systemic medication (SM)+BLT, 400 patients (41.9%) received SM only, and 29 patients received BLT only (3.0%). SM+BLT cohort was associated with longer median overall survival (mOS) than the SM only and the BLT only cohorts both in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)-negative/unknown patients (15.3 months, 95% confidence interval [CI], 14.2-16.4; 11.1 months, 9.0-13.2; 7.0 months, 5.4-8.6; p<0.001) and in EGFR/ALK-positive patients (33.7 months, 28.5-38.9; 22.1 months, 17.8-26.4; 4.0 months, 3.6-4.4; p < 0.001). As for timing of radiotherapy, SM+EBR (14.1 months, 12.7-15.5) was associated with inferior mOS than SM+DBR (19.4 months, 14.2-24.6) in EGFR/ALK-negative/unknown patients. No significant difference was found in EGFR/ALK-positive patients (28.3 months, 19.1-37.5; 33.3 months, 28.1-38.5). Patients in the EGFR/ALK-negative/unknown cohort treated with first-line pemetrexed with platinum (PP) (15.8 months, 14.0-17.6, p<0.001) had longer mOS than those received non-PP regimens (13.1 months, 11.6-14.6). However, no difference was observed among EGFR/ALK-positive patients who were treated with tyrosine kinase inhibitors (TKIs) (29.5 months, 21.1-37.9; p = 0.140), PP (27.2 months, 21.6-32.8) and non-PP regimens (25.0 months, 16.0-34.0). CONCLUSIONS: Our study confirmed that the use of SM+BLT is associated with superior mOS than those treated with SM only and BLT only. SM+DBR might be a better radiotherapeutic strategy for this patient population. EGFR/ALK-negative/unknown patients showed a survival benefit with PP treatment.

The efficacy of first-line chemotherapy in recurrent or metastatic nasopharyngeal carcinoma: a systematic review and meta-analysis.

BACKGROUND: The standard first-line chemotherapy for patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has not been well established. We conducted a pooled meta-analysis to evaluate the efficacy of commonly used first-line chemotherapy in this disease. METHODS: Electronic databases including PubMed, Embase, and Corchrane library were searched for eligible literatures. Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS) were pooled with the 95% confidence interval (CI) using R software. RESULTS: Totally 973 patients were available for analysis from 14 phase II single arm clinical trials and 2 phase III randomized clinical trials. Four regimens were identified including 5-fluorouracil plus platinum (FP), gemcitabine plus platinum (GP), taxanes plus platinum (TP), and triplet combination regimen. Of these four regimens, triplet combination regimen demonstrated best short-term efficacy with a highest ORR (0.74; 95% CI, 0.62-0.87), DCR (0.91; 95% CI, 0.87-0.95), and 6-month PFS rate (0.83; 95% CI, 0.75-0.91), while 1-year OS rate (0.74; 95% CI, 0.61-0.87) was a little lower than TP regimen. Meanwhile, TP regimen showed best prognosis with a highest 1-year OS rate of 0.79 (95% CI, 0.65-0.92) and pretty good short-term efficacy with an ORR of 0.60 (95% CI, 0.48-0.72) and a DCR of 0.92 (95% CI, 0.86-0.98) comparable with triplet combination therapy. FP regimen had the lowest ORR (0.52; 95% CI, 0.38-0.65) and 1-year OS rate (0.63; 95% CI, 0.57-0.69). Efficacy of GP regimen fell between FP and TP regimens with an ORR of 0.54 (95% CI, 0.38-0.65), a DCR of 0.85 (95% CI, 0.71-0.93), a 6-month PFS rate of 0.69 (95% CI, 0.60-0.78) and a 1-year OS rate of 0.71 (95% CI, 0.61-0.80). CONCLUSIONS: Among four commonly used first-line chemotherapy regimens for R/M NPC, triplet combination regimen showed best short-term efficacy but failed to improve prognosis. TP regimen demonstrated fairly good short-term efficacy and best long-term efficacy, followed by GP regimen, while FP regimen was the lowest.

Establishment of an Adjusted Prognosis Analysis Model for Initially Diagnosed Non-Small-Cell Lung Cancer With Brain Metastases From Sun Yat-Sen University Cancer Center.

BACKGROUND: The current published prognosis models for brain metastases (BMs) from cancer have not addressed the issue of either newly diagnosed non-small-cell lung cancer (NSCLC) with BMs or the lung cancer genotype. We sought to build an adjusted prognosis analysis (APA) model, a new prognosis model specifically for NSCLC patients with BMs at the initial diagnosis using adjusted prognosis analysis (APA). PATIENTS AND METHODS: The model was derived using data from 1158 consecutive patients, with 837 in the derivation cohort and 321 in the validation cohort. The patients had initially received a diagnosis of BMs from NSCLC at Sun Yat-Sen University Cancer Center from 1994 to 2015. The prognostic factors analyzed included patient characteristics, disease characteristics, and treatments. The APA model was built according to the numerical score derived from the hazard ratio of each independent prognostic variable. The predictive accuracy of the APA model was determined using a concordance index and was compared with current prognosis models. The results were validated using bootstrap resampling and a validation cohort. RESULTS: We established 2 prognostic models (APA 1 and 2) for the whole group of patients and for those with known epidermal growth factor receptor (EGFR) genotype, respectively. Six factors were independently associated with survival time: Karnofsky performance status, age, smoking history (replaced by EGFR mutation in APA 2), local treatment of intracranial metastases, EGFR-tyrosine kinase inhibitor treatment, and chemotherapy. Patients in the derivation cohort were stratified into low- (score, 0-2), moderate- (score, 3-5), and high-risk (score 6-7) groups according to the median survival time (16.6, 10.3, and 5.2 months, respectively; P < .001). The results were further confirmed in the validation cohort. CONCLUSION: Compared with recursive partition analysis and graded prognostic assessment, APA seems to be more suitable for initially diagnosed NSCLC with BMs.

Long-lasting response to third-line crizotinib treatment in a patient with non-small cell lung cancer with brain metastases and poor performance status.

Identification of the anaplastic lymphoma kinase (ALK) gene has refined the classification of non-small cell lung cancer (NSCLC) and promoted research on molecularly targeted drugs such as crizotinib, an ALK inhibitor with good efficacy, in ALK-rearranged NSCLC. At present, few studies have reported the efficacy of crizotinib in patients with ALK-rearranged NSCLC with brain metastases. In a patient with NSCLC harboring ALK-rearrangement who had brain metastases and poor performance status (PS), we obtained a durable response with crizotinib administered following multi-line chemotherapy regimens.

Consolidation chemotherapy improves progression-free survival in stage III small-cell lung cancer following concurrent chemoradiotherapy: a retrospective study.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for limited-stage small-cell lung cancer (LD-SCLC). However, the efficacy of consolidation chemotherapy (CCT) in LD-SCLC remains controversial despite several studies that were performed in the early years of CCT use. The aim of this study was to reevaluate the effectiveness and toxicities associated with CCT. METHODS: This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small-cell lung cancer (SCLC) who underwent CCRT from January 2001 to December 2013 at Sun Yat-Sen University Cancer Center (SYSUCC). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier methods. Univariate and multivariate analyses were performed to analyze patient prognosis factors. RESULTS: Among the 177 patients, 72 (41%) received CCT and 105 (59%) did not receive CCT. PFS was significantly better for patients in the CCT group compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9 months, respectively, P=0.031), whereas the differences in OS were not statistically significant (median OS: 31.6 vs 24.8 months, respectively, P=0.118). The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT group and 27.6% and 6.7% for patients in the non-CCT group, respectively. Multivariate analysis revealed that having a pretreatment carcinoembryonic antigen level <5 ng/mL (P=0.035), having undergone prophylactic cranial irradiation (P<0.001), and having received CCT (P=0.002) could serve as favorable independent prognostic factors for PFS. Multivariate analysis for OS also showed that having undergone PCI (P<0.001) and having received CCT (P=0.006) were independent significant prognostic factors. CONCLUSION: CCT can improve PFS for patients with stage IIIA and IIIB SCLC following CCRT without significantly increasing treatment-related toxicities.

Blood-brain barrier permeability of gefitinib in patients with brain metastases from non-small-cell lung cancer before and during whole brain radiation therapy.

INTRODUCTION: To explore the ability of gefitinib to penetrate blood brain barrier (BBB) during whole brain radiation therapy (WBRT). PATIENTS AND METHODS: Enrolled in this study were eligible patients who were diagnosed with BM from NSCLC. Gefitinib was given at 250 mg/day for 30 days, then concurrently with WBRT (40 Gy/20 F/4 w), followed by maintenance. Serial CSF and blood samples were collected on 30 day after gefitinib administration, and at the time of 10, 20, 30 and 40 Gy following WBRT. CSF and plasma samples of 13 patients without BM who were treated with gefitinib were collected as control. CSF and plasma gefitinib levels were measured by LC-MS/MS. RESULTS: Fifteen BM patients completed gefitinib plus WBRT. The CSF-to-plasma ratio of gefitinib in patients with BM was higher than that in patients without BM (1.34% vs. 0.36%, P < 0.001). The CSF-to-plasma ratio of gefitinib increased with the increased dose of WBRT and reached the peak (1.87 ± 0.72%) at 30 Gy, which was significantly higher than that 1.34 ± 0.49% at 0 Gy (P = 0.01). The median time to progression of brain lesions and the median overall survival were 7.07 and 15.4 months, respectively. CONCLUSION: The BBB permeability of gefitinib increased in accordance with escalated dose of WBRT.

[Impacts of yin-yang meridians acupuncture with respiratory reinforcing and reducing manipulation on lower limbs balance function in stroke patients].

OBJECTIVE: To observe the impact on lower limbs balance function in treatment of yin-yang meridians acupuncture with respiratory reinforcing and reducing manipulation involved in the patients of stroke by applying B-PHY balance function test training system so as to provide the objective evidence in treatment of stroke; with acupuncture. METHODS: One hundred patients were randomized into an observation group and a control group, 50 cases in each one. In the control group, the basic treatment was applied, without other relevant rehabilitation therapies associated. In the observation group, with the basic treatment as the control group's, the therapy of the yin-yang meridians acupuncutre with respiratory reinforcing and reducing manipulation was adopted. On the yin meridians, Zuwuli (LR 10), Xuehai (SP 10), Yinlingquan (SP 9), Sanyinjiao (SP 6) and the others were selected and stimulated with reducing manipulation achieved by the coordination of patient's respiration. On the yang meridians, Biguan (ST 31), Liangqiu (ST 34), Yanglingquan (GB 34) and the others were selected and stimulated with reinforcing manipulation achieved by the coordination of patient's respiration. The treatment was given once a day and for 28 days totally. Before treatment and in 28 days of treatment, B-PHY balance function test training system was used to determine the weight shift track parameters (track length, peripheral square, track length of per unit square, left-right offset and rectangle square), the weight shift track distance parameters [mean of X axle weight shift distance (Mean-X), mean of Y axle weight shift distance (Mean-Y), maximum of X axle weight shift distance (Max-X), maximum of Y axle weight shift distance (Max-Y), weight shift distance (LSKG), weight shift square (SSKG), square ratio of weight shift (LFS)], stability coefficient (SI) and weight distribution coefficient (WDI). RESULTS: After treatment, the differences in the weight shift track parameters, SI and WDI were significant as compared with those before treatment in the patients of the two groups (all P<0.01); while the differences in the weight shift distance parameters in the observation group were improved obviously after treatment as compared with those before treatment (all P<0.01), the differences of Mean-X, Max-Y and LFS in the control group were improved after treatment as compared with those before treatment (all P<0.01). Except SSKG, the improvements after treatment in the rest indices in the observation group were better than those in the control group (all P<0.05). CONCLUSION: The yin-yang meridians acupuncture with respiratry reinforcing and re- ducing manipulation effectively improves the lower limbs balance function in the patients of stroke.

[Efficacy observation on wrist-ankle needle for primary dysmenorrhea in undergraduates].

OBJECTIVE: To compare efficacy difference among wrist-ankle needle, body-acupuncture and ibuprofen in the treatment of primary dysmenorrhea. METHODS: Ninety-five cases were randomly divided into a wrist-ankle needle group (32 cases), a body-acupuncture group (31 cases) and an ibuprofen group (32 cases). Acupunc- , ture at Lower 1 and Lower 2 area was applied in the wrist-ankle needle group. Acupuncture at Guanyuan (CV 4) and Sanyinjiao (SP 6) were applied in the body-acupuncture group. Ibuprofen sustained-release capsules were given for oral administration in the ibuprofen group. The treatment began 3 days before menses, once a day, until pain was relieved. One menstrual cycle was taken as a treatment course, continuously for 3 courses and efficacy were observed in three groups. The symptom score of dysmenorrhea and visual analogue scale (VAS) were used to assess pain severity before and after treatment. RESULTS: 1The efficacy differences in three groups were statistically significant (P<0.01), in which the total effective rate was 90. 0% (27/30) in the wrist-ankle needle group, 73.4% (22/30) in the body-acupuncture group and 46. 7% (14/30) in the ibuprofen group. 2 After the treatment, symptom score of dysmenorrhea and VAS were all obviously lower than that before the treatment in three groups (all P<0.01). Compared with ibuprofen group (7.12+/-2.70), after the treatment symptom score of dysmenorrhea in the wrist-ankle needle group (4.00+/-3.40) and body-acupuncture group (5. 53+/-2. 80) was obviously decreased (P<0.01, P<0.05), and VAS in the wrist-ankle needle group was significantly reduced (P<0.05). Compared with body-acupuncture group (5. 53+/-2.80), symptom score of dysmenorrhea in the wrist-ankle needle group (4.00+/- 3. 40) was obviously decreased (P<0. 05). CONCLUSION: The wrist-ankle needle has better effect than body acupuncture and ibuprofen on the treatment of primary dysmenorrhea, which could significantly improve dysmenorrhea symptoms.

[Effect of moxibustion at sanyinjiao (SP 6) on the process of childbirth: a randomized controlled study].

OBJECTIVE: To explore the effect of moxibustion at Sanyinjiao (SP 6) on normal process of childbirth and safety of mothers and infants. METHODS: One hundred and seventy-four cases of singleton primiparas, fetal head position were selected as the subjects and divided into three groups by single-blind randomized method: an acupoint group (n = 59), a non-acupoint group (n = 57) and a blank group (n = 58). When the cervix was dilated by 2 to 3 cm, DAJ-23 type multi-function moxibustion apparatus was used at Sanyinjiao (SP 6) in acupoint group, and at non-acupoint spot (the midpoint from the radial arterial pulse throbbing place on the radial side of the transverse crease of the wrist to the radial end of biceps tendon of the elbow) in non-acupoint group, 30 min for each one. The conventional labor care was adopted in blank group. The differences were observed in the first active stage, the second stage and the third stage of the labor as well as the safety of mothers and infants among three groups. RESULTS: The durations of the first active stage of labor [(123.05 +/- 96.401) min] and the second stage [(37.407 +/- 22.390) min] in acupoint group were shorter than those [(171.40 +/- 94.339) min, (49.517 +/- 25.373) min] in non-acupoint group, as well as those [(178.79 +/- 97.231) min, (53.684 +/- 20.087) min] in blank group separately (all P < 0.05). It was discovered that the progressions of the first active stage and the second stage of labor were accelerated in acupoint group, and there was no statistically significant difference in the third stage of labor among the three groups (all P > 0.05). Bleeding amount after childbirth in acupoint group was less than those in non-acupoint group and blank group (both P < 0.05), and Apgar scores of newborns in acupoint group and non-acupoint group were higher than that in blank group (both P < 0.05). CONCLUSION: Moxibustion at Sanyinjiao (SP 6) can shorten the process of childbirth, reduce postpartum bleeding and has no harmful impact on mothers and infants.

[Effect of moxibustion at Sanyinjiao (SP 6) on delivery stage and postpartum bleeding of primipara].

OBJECTIVE: To observe the effect of moxibustion at Sanyinjiao (SP 6) on delivery stage of primipara. METHODS: Sixty cases of primipara were divided into a moxibustion at Sanyinjiao group, a non-acupoint group and a blank group. When the diameter of wormb mouth opened to 2-3 cm, showing that it entered into active stage of uterine contraction, moxibustion at Sanyinjiao (SP 6) for primipara was applied in moxibustion at Sanyinjiao group; moxibustion was applied at 1 cun towards radialis from the region where 2 cun above Kongzui (LU 6) in non-acupoint group, 30 minutes treatment was for both groups. There was no intervention in blank group. After delivery, the time of first,second and third delivery stages and postpartum bleeding 2 hours after delivery were compared among three groups. RESULTS: The active duration of first delivery stage in moxibustion at Sanyinjiao group was significantly shorter than that in the other two groups (P < 0.05, P < 0.01); the duration of the second delivery stage in moxibustion at Sanyinjiao group was significantly shorter than that in the other two groups (both P < 0.05) as well; the postpartum bleeding 2 hours after delivery in moxibustion at Sanyinjiao group was less than other two groups and the difference was statistic significant between moxibustion at Sanyinjiao group and blank group (P < 0.05). CONCLUSION: By moxibustion at Sanyinjiao (SP 6), the active duration of first delivery stage and the duration of second delivery stage are markedly shortened, postpartum bleeding 2 hours after delivery is obviously reduced, and the safety of vaginal delivery is increased.

Effect of acupoint Sanyinjiao (SP6) moxibustion on the first stage of labor and uterine contractive pain in primiparae.

OBJECTIVE: To observe the effect of acupoint Sanyinjiao (SP6) moxibustion (S-Mox) on the duration of the first labor stage and uterine contractive pain in primiparae. METHODS: Sixty primipara women in labor were equally assigned according to their choice to three groups: women in the S-Mox group received bilateral S-Mox for 30 min, women in the non-acupoint group received moxibustion (Mox) applied on non-acupoints for 30 min, and those in the control group did not receive Mox intervention. The duration of the first labor stage was recorded and the degree of labor pain was estimated by a visual analogue scale (VAS) before and after Mox. RESULTS: The duration of the first stage active phase in the S-Mox group was significantly shorter than that in the other two groups (P<0.05, P<0.01); the VAS score after Mox was lower in the S-Mox group, showing a statistical difference in comparison with the control group (P<0.05). CONCLUSIONS: Applying S-Mox could markedly shorten the active phase of the first stage of labor and lower the VAS score of uterine contractive pain, which means alleviating the pain caused by vaginal delivery. Its mechanism is worthy of further study.

[Discussion on the acupuncture and constitution according to the Miraculous Pivot].

The texts on constitution of Miraculous Pivot were analyzed and summarized according to literature study. The findings show that constitution is an important element in acupuncture treatment according to the texts of Miraculous Pivot. Different constitution generates the difference of yin-yang, deficiency or excess of qi and blood which is the important basis for syndrome differentiation of Miraculous Pivot. Therefore, the improvement in constitution is the way to increase the therapeutic effect of acupuncture.

[Effect on moxibustion at Sanyinjiao (SP 6) for uterine contraction pain in labor: a randomized controlled trial].

OBJECTIVE: To investigate the effect of moxibustion at Sanyinjiao (SP 6) for uterine contraction pain in labor, and evaluate the safety of the parturient and newborn. METHODS: One hundred and seventy-four cases of singleton pregnancy and cephalic presentation primipara were single blinded and randomly divided into three groups: observation group (59 cases), placebo treated group (57 cases) and blank group (58 cases). The observation group was treated with moxibustion at Sanyinjiao (SP 6) for 30 min when the uterus cervix openning at 3 cm, the placebo treated group was treated with moxibustion at no acupoint for 30 min and the blank group was treated with routine labor nursing, the uterine contraction pain and the safety of the mother and infant were compared among three groups. RESULTS: 1) The uterine contraction pain was tested by Visual Analogue Scale (VAS): the scores of VAS in the observation group were obviously decreased after 15 min and 30 min of moxibustion (both P<0.05), there were no obvious changes of the VAS scores in placebo treated group and the blank group, the scores of VAS in observation group decreased much more obviously than those in the other two groups (all P<0.05); 2) Midwife rating of the uterine contraction pain: after 30 min of moxibustion, the effective rate of labor analgesia was 69.5% (41/59) in observation group, which was higher than that of 45.6% (26/57) in placebo treated group and 43.1% (25/58) in blank group, with significant differences between them (both P<0.05); 3) The postpartum hemorrhage amount of the observation group was obviously lower than those of placebo treated group and blank group (both P<0.05); 4) The Apgar score of newborn was higher in observation group and placebo treated group than that of blank group (both P<0.05). CONCLUSION: Moxibustion at Sanyinjiao (SP 6) can relieve the uterine contraction pain, and has no side effect to mother and infant, it is one of the safe, effective and simple non-drug analgesia methods.

[Effect of needling "Housanli" (ST 36) with different retaining-needle time on the pain threshold of mice using the hot water tail-flick test].

OBJECTIVE: To observe the effect of needling "Housanli" (ST 36) with different retaining-needle time on the pain threshold of mice using the hot water tail-flick test, and investigate the relationship between the retaining-needle time and the therapeutic effect. METHODS: Twenty-four healthy mice were randomly divided into four groups: no retaining-needle group (group A), retaining-needle 10 min group (group B), retaining-needle 20 min group (group C) and retaining-needle 30 min group (group D), with 6 mice for each group. After acupuncture "Housanli", the tail of mouse was put into the hot water at 50 degrees C, and the intervening time from the tail entered water to the tail flicked out of water was recorded and analyzed for each group. RESULTS: After acupuncturing "Housanli", the pain threshold was significantly improved with the hot water tail-flick test in both group A and group C (both P<0.01), however, there was no significant difference in both group B and group D (both P>0.05). Within 30 min of retaining-needle, the effect curve of acupuncture analgesia was showed in a waved line. In contrast, the maximum value of latent period on the tail-flick was detected in the group C that was the biggest effect of acupuncture analgesia among the four groups. CONCLUSION: The best retaining-needle time of hand-acupuncture for acupuncture analgesia is 20 min.