The efficacy and safety of apatinib plus capecitabine in platinum-refractory metastatic and/or recurrent nasopharyngeal carcinoma: a prospective, phase II trial.

BACKGROUND: Previous studies have shown that monotherapy with apatinib, an oral tyrosine kinase inhibitor, has promising efficacy for treating recurrent or metastatic (RM) nasopharyngeal carcinoma (NPC) patients. In this study, we aimed to assess the efficacy and safety of apatinib combined with capecitabine as a second-line therapy or beyond for treating RM-NPC patients who failed the first-line platinum-based chemotherapy. METHODS: In this single-arm, phase II study, we enrolled RM-NPC patients who had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The sample size was determined using Simon's two-stage design. All patients were administered with apatinib 500 mg once daily and capecitabine 1000 mg/m2 twice per day on days 1-14 of each 21-day cycle. The primary endpoint was the objective response rate (ORR), and the secondary endpoints comprised disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: We enrolled 64 patients from September 2018 to August 2020. The ORR and DCR were 39.1% (95% CI, 27.1-52.1) and 85.9% (95% CI, 75.0-93.4), respectively. The median DoR was 14.4 months (95% CI, 7.8-21.0). As of April 20, 2021, the median follow-up duration was 12.0 months. The median PFS was 7.5 months (95% CI, 5.0-10.0) and the median OS was 15.7 months (95% CI, 11.3-20.1). The most common toxicities of any grade were anemia (75.0%), hand-foot syndrome (65.6%), and proteinuria (64.0%). Grade 3-4 toxicities were observed in 36 (56.3%) patients, with hypertension (14.1%), mucositis (12.4%), and fatigue (10.9%) most commonly observed. CONCLUSIONS: Apatinib plus capecitabine shows promising efficacy as a second-line treatment option in pretreated platinum-refractory RM-NPC patients. Dose selection of this combination needs further investigation considering the toxicity. TRIAL REGISTRATION: Chi-CTR1800017229.

Initial Progression-Free Survival after Non-First Line TKIs Therapy Potentially Guides Immediate Treatment after Its Failure in Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: The standard therapy after failure of the initial non-first line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in advanced non-small cell lung cancer (NSCLC) has not yet been established. The aim of the current study was to identify whether the 2(nd) TKI treatment or chemotherapy (paclitaxel-containing or non-paclitaxel regimen) is the appropriate treatment for patients with NSCLC based on the efficacy of the initial TKIs. METHODS: Seventy-two advanced NSCLC patients who had accepted 2(nd) TKIs or chemotherapy immediately after failure of the initial TKIs in non-first line setting from May 1, 2004 to January 31, 2010 at the Sun Yat-sen University Cancer Center were enrolled. The primary endpoint [2(nd) progression-free survival (PFS)] and the second endpoint [overall survival (OS)] were compared among the 2(nd) TKI and chemotherapy groups as well as their subgroups. RESULTS: (1) Twenty-one patients were treated with 2(nd) TKIs, and 51 patients were administered chemotherapy after failure of the initial non-first line TKI treatment. There was nonsignificant difference in the responses (P=0.900) [2(nd) PFS (P=0.833) and OS (P=0.369)] between the 2(nd) TKI and chemotherapy groups. (2) In the 2(nd) TKI group, 9 patients exhibited PFS≥7 months. The initial TKI treatment group exhibited a longer 2(nd) PFS than the other 12 patients with an initial PFS<7 months (7 months vs. 2 months, P=0.019). However, these groups had nonsignificantly different OS (P=0.369). (3) In the chemotherapy group, patients with PFS<5 months exhibited longer 2(nd) PFS than those with PFS ≥ 5 months in the initial TKI treatment (3 months vs. 2 months, P=0.039). (4) In the chemotherapy group, patients treated with paclitaxel-containing regimen showed longer 2(nd) PFS than those treated with non-paclitaxel regimen (5 months vs. 2.3 months, P=0.043). CONCLUSIONS: Patients with PFS≥7 months or <5 months under the initial TKI treatment potentially benefit from the 2(nd) TKI treatment or chemotherapy immediately after failure of the non-first line TKIs. The paclitaxel-containing regimen may improve the 2(nd) PFS. However, more patient samples are urgently needed to validate these findings.

Short-term outcomes of cetuximab combined with standard chemotherapy as first line setting for Chinese patients with non-small cell lung cancer: a report of 12 cases.

Cetuximab combined with chemotherapy has been used to treat Non-small cell lung cancer (NSCLC) in recent years, however, the data from China was rare. This study was to summarize our experiences in treating NSCLC patients with cetuximab in the first line setting. From October 1st 2006 to Jun 30th 2010, twelve NSCLC patients were treated with cetuximab combined standard chemotherapy as first line setting in Sun Yat-sen University Cancer Center entered the study and the short-term efficacy and safety were analyzed. A total of 132 cycles of cetuximab treatment, with a median of nine cycles in the whole group were administered. The ORR was 41.7% (5/12), DCR was 83.3% (10/12), median TTP was 5.5 months (2-23), and median OS was 9 months (2-48) in the whole group. There were 75% (9/12) patients occurred acne-like rash within first 3 weeks, their ORR was 55.6% (5/9), DCR was 100% (9/9), however, ORR and DCR in patients who didn't occurred acne-like rash within first 3 weeks were 0 and 33.3% (1/3), the difference ORR between two group was insignificant (P = 0.091), however, DCR was significant different (P = 0.007). There no treatment-associated death and no cetuximab-associated discontinuation. The incidence of acne-like rash was 83.3% (10/12) and 75% (9/12) occurred within first 3 weeks, there were eight patients suffered side effects associated with chemotherapy. So we can draw a conclusion that the short-term outcome of cetuximab application in first line setting for patients with NSCLC were promising since the higher ORR and DCR, especially those occurred acne-like rash within the first 3 weeks, and the addition of cetuximab in this population was safe.

[Short-term efficacy of cetuximab combined with radiotherapy or chemotherapy on head and neck cancer: a report of 11 cases].

BACKGROUND AND OBJECTIVE: Cetuximab combined with radiotherapy or chemotherapy has been used to treat head and neck cancer in recent years, but few reports are available in China now. This study was to summarize our experiences in treating patients with head and neck cancer cetuximab. METHODS: From October 1st, 2005 to September 30th, 2008, six with patients head and neck cancer were treated using cetuximab combined with radiotherapy and five were treated using cetuximab combined with chemotherapy in Sun Yat-sen University Cancer Center. The short-term efficacy and safety were analyzed. RESULTS: A total of 82 cycles of cetuximab treatment, with a median of seven cycles, were administered safely. There was no treatment-associated death and no cetuximab-associated discontinuation. In cetuximab combined with radiotherapy group, four patients achieved complete response (CR) and two achieved partial response (PR); all CR patients had hadacne-like rash (three cases were > or = grade III), only one PR patient had grade I rash; five patients had skin reaction in the irradiation field (four cases of skin reaction were > or = grade III); hematological toxicity was slight excepted one case of grade IV. In cetuximab combined chemotherapy group, two patients achieved PR, two had stable disease (SD) and one had progressed disease (PD); the of acne-like rash was low, and three patients experienced bone marrow depression above grade III. CONCLUSION: Cetuximab combined with either radiotherapy or chemotherapy are good options for suitable patients with head and neck cancer.

[Observation of clinical response of "sheng ban recipe" for platelets decrease after chemotherapy].

BACKGROUND & OBJECTIVE: The majority of cancer chemotherapy can lead to bone marrow depression, which often affects clinical response as chemotherapy can not be carried out with enough dosage on time. The platelets decrease is one of the problems caused by bone marrow depression. Though the clinical response of hyodermic "IL-11" is affirmed to advance platelets presently, it is limited by expensive price. Other agents that can be taken orally with suitable price and equal authenticity are less reported. The author observed clinical response of platelets decrease adopting traditional Chinese medicine "Sheng Ban Recipe"(SBR). METHODS: Totally 103 patients with platelets decrease after chemotherapy from July 1994 to Jannary 2002. They were randomly divided into two groups: SBR plus common treatment group and common treatment alone group. The previous group take 1 package SBR for twice drink per day. Common treatment group give common therapy only. The follow-up period is 2 weeks. RESULTS: Among the 55 cases in SBR group, noticeable efficiency 20%, efficiency 50.9%, total efficiency 70.9%, which is evidently superior to common group. CONCLUSION: "Sheng Ban Recipe" can effectively treat thrombocytopenia after chemotherapy, which helps to reduce the necessary of intravenous drip of platelets and the risk of hemorrhage.

[Clinical study in prophylactic use of chinese medicine to prevent chemoradiotherapy induced mucositis in nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Oropharyngeal mucositis is the most common acute non-hematology toxicity in nasopharyngeal carcinoma (NPC) treated with radiotherapy, especially in the concomitant chemoradiotherapy of local advanced NPC patients. This study was designed to observe the effect of traditional Chinese medicine against acute oropharyngeal mucositis from chemoradiotherapy in patients with local advanced NPC. METHODS: A total of 101 patients in stage III- IVa (Fuzhou 1992) were enrolled into this prospective randomized clinical trial. The cases were divided into treatment group (52 cases) and control group (49 cases). The median doses were 70.31+/-1.21 Gy for the treatment group and 70.78+/-1.95 Gy for the control group, respectively. Chemotherapy was concomitant with radiotherapy [single agent cisplatin (DDP,30 mg/m(2)) 6 times from first to sixth week of radiotherapy duration]. The patients of treatment group took 5-8 times of Chinese medicine daily and those of control group took 5-8 times of Dobell's solution daily.The observation indices included the degree of oropharyngeal and hematological toxicity, radiotherapy duration, and curative effect. RESULTS: (1)Oropharyngeal toxicity: there was no 0 degree oropharyngeal toxicity in both groups, I degree toxicity in 29 cases (55.77%) and 2 cases (4.08%), II degree toxicity in 18 cases (34.62%) and 17 cases (30.69%), III degree toxicity in 5 cases (9.62%) and 22 cases (44.89%), IV degree toxicity in 0 case (0%) and 8 cases (16.33%); there was statistical significance of difference between the two groups (P=0.000). (2)Hematological toxicity: there was no IV degree hematological toxicity in both groups. WBC toxicity (Z=-0.604,P=0.546), neutrophilic granulocyte toxicity (Z=-0.226,P=0.821), and platelet toxicity (Z=-0.099,P=0.922) were compared; there was no statistic significance of difference (P >0.05); (3)Radiotherapy duration: The radiotherapy duration of two groups were 49.79+/-1.83 days and 51.00+/-4.46 days; there was no statistic significance of difference (P=0.082). (4)Curative effects: The curative effects of two groups were:complete remission (CR) 76.92% (40/52) and 69.39% (34/49), partial remission (PR) 23.08% (12/52) and 30.61% (15/49); there was no statistical significance of difference (P=0.392). CONCLUSION: Chinese medicine was effective in reducing acute oropharyngeal toxicity resulting from chemoradiotherapy in patients with local advanced NPC. Furthermore, the apparent side effects of Chinese medicine in this study have not been observed. Chinese medicine treatment did not affect the short-term clinical outcome.

[Preliminary report of semimonthly 5-fluorouracil/leucovorin combined with paclitaxel in treatment of advanced gastric cancer (AGC)].

BACKGROUND & OBJECTIVE: Phase II clinical trails showed that paclitaxel is effective in treatment of advanced gastric cancer (AGC). The combination of paclitaxel and 5-fluorouracil (5-FU) in the treatment of advanced gastric cancer is effective and safe. This study was designed to evaluate the efficacy and the toxicity of paclitaxel combined with semimonthly 5-FU/Leucovorin for the AGC patients. METHODS: Twenty-five measurable patients with AGC proved pathologically were enrolled into this study. The chemotherapy regimen was comprised of paclitaxel,75 mg/m(2) i.v. in a 3-hour infusion followed by 2-hour infusion of leucovorin 200 mg/m(2), then 10-minute intravenous bolus of 5-FU 375 mg/m(2), then 48-hour infusion of 5-FU 2.8 g/m(2) using an ambulatory pump. The regimen was given per 14 days. One cycle consisted of twice chemotherapy regimens. All enrolled patients received at least two cycles of treatment. RESULTS: After two cycles of chemotherapy, the complete remission and the partial remission were 8% and 60%, respectively. The median duration of response was 4 months. No treatment-related death occurred. Phlebitis,feeling disorder, and alopecia were main side effects. CONCLUSION: Semimonthly 5-FU/LV combined with paclitaxel has high release rate but comparatively mild toxicity for AGC patients.