Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. METHODS: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. FINDINGS: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. INTERPRETATION: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. FUNDING: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Comparison of radiotherapeutic management of operated breast cancer in 1999 and in 2006: a sampling survey on the southeast coast of China.

AIMS: To obtain a better understanding of the changes in radiotherapeutic management of breast cancer patients in the more developed areas of China over the past decade. METHODS: Four academic radiation therapy departments located on the Southeast Coast of China were selected for the study. The survey was conducted on female breast cancer patients who received radiotherapy in 1999 and 2006. The questionnaires were designed to determine the purposes of radiotherapy and to address the postoperative radiotherapy techniques used. The data for these two years were analyzed and compared. RESULTS: The percentage of breast-conserving treatment increased from 3% in 1999 to 13% in 2006, but the percentage of patients treated with postmastectomy radiotherapy dropped from 69% in 1999 to 66% in 2006 (P < 0.05). As regards the changes in techniques from 1999 to 2006, the use of special immobilization devices, treatment planning systems, and CT simulations increased from 46% to 80%, 23% to 70%, and 0% to 14%, respectively (P <0.01). From 1999 to 2006, irradiation of the chest wall following mastectomy increased from 67% to 90%, but for internal mammary irradiation it decreased from 76% to 30% and for the axilla, from 69% to 37% (P < 0.01). There were no obvious differences between 1999 and 2006 on the field design, boost treatment on the tumor bed, or dose prescription. CONCLUSIONS: Breast-conserving treatment was performed more frequently in China in 2006 than in 1999, but postmastectomy radiotherapy did not change a great deal and it was still an essential option. Although the international treatment guidelines have been accepted and implemented by physicians in recent years, prompt improvement in the quality of breast cancer radiotherapy is needed.

Efficacy and safety of nimotuzumab in addition to radiotherapy and temozolomide for cerebral glioblastoma: a phase II multicenter clinical trial.

Background: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) antibody that has shown preclinical and clinical anticancer activity in cerebral glioblastoma multiforme (GBM). We conducted a phase II, single-arm, multicenter clinical trial to evaluate the benefit of adding nimotuzumab to current standard chemo-radiotherapy for patients with GBM with positive EGFR expression. Methods: Newly diagnosed patients with histologically proven single supratentorial GBM and epidermal growth factor receptor (EGFR) positive expressions were recruited. All patients were treated with nimotuzumab, administered once a week intravenously for 6 weeks in addition to radiotherapy with concomitant and adjuvant temozolomide after surgery. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary objectives included objective response rate (ORR) and toxicity. Results: A total of 39 patients were enrolled and 36 patients were evaluated for efficacy. The ORR at the end of RT was 72.2%. Median OS and PFS were 24.5 and 11.9 months. The 1-year OS and PFS rates were 83.3% and 49.3%. The 2-year OS and PFS rates were 51.1% and 29.0%. O (6)-methylquanine DNA methyl-tranferase (MGMT) expression is known to affect the efficacy of chemotherapy and status of its expression is examined. No significant correlation between treatment outcomes and MGMT status was found. Most frequent treatment-related toxicities were mild to moderate and included constipation, anorexia, fatigue, nausea, vomiting, and leucopenia. Conclusions: Our study show that nimotuzumab in addition to standard treatment is well tolerable and has increased survival in newly diagnosed GBM patients with EGFR positive expression.

[Expressions of P16 and nm23-H1 in nasopharyngeal cacinoma and their clinical significance].

OBJECTIVE: To examine the expressions of P16 and nm23-H(1) protein in nasopharyngeal carcinoma (NPC) and explore their association with clinicopathology and the level of argyrophilic protein of the nucleolar organizer regions (AgNORs) of peripheral blood T lymphocyte (T-AgNORs) before radiotherapy. METHODS: SP immunohistochemistry was used to detect P16 and nm23-H(1) expressions in 65 cases of NPC, and the level of T-AgNORs was measured before radiotherapy. RESULTS: The positivity rate of P16 and nm23-H(1) protein in NPC was 24.6% (16/65) and 61.5% (40/65), respectively. The positivity rates of P16 and nm23-H(1) protein in patients in T(1) and T(2) stages were higher than those in patients in T(3) and T(4) stages, but the difference was not statistically significant (P>0.05). No significant association of P16 expression was noted with lymph node metastasis and post-radiotherapy distant metastasis (P>0.05). In patients with regional lymph node and distant metastases, the positivity rates for nm23-H(1) were 51.2% (21/41) and 33.3% (5/15), which were significantly lower than those in patients without local lymph node (79.2%, 9/24;X(2)= 4.99, P<0.05) or distant metastasis (70%, 35/50; X(2)=7.56, P<0.01). The levels of T-AgNORs in P16- and nm23-positive cases were higher than those in the negative cases (t=5.721, P<0.001). CONCLUSIONS: nm23-H(1) expression in NPC tissue is correlated with NPC metastasis and may be useful for clinical prediction of local lymph node and distant metastases after radiotherpay. nm23 and p16 expressions are also correlated with the level of T-AgNORs, which probably indicate the immune functions of the patients.