EGFR mutations are effective predictors for gefitinib efficacy in Chinese patients with advanced NSCLC. HER2 and HER3 expression does not provide any additional information for selecting patients most likely to benefit from gefitinib treatment.
BackgroundBasic research of gefitinib (Iressa, ZD1839) has demonstrated the combination effects of gefitinib and chemotherapy were sequence-dependent. To evaluate the efficacy of sequential administration of gefitinib following a minor response or partial response to two to three cycles of chemotherapy, a phase II clinical trial was done in Chinese patients with advanced non-small-cell lung cancer (NSCLC).MethodsThirty-three consecutive patients with advanced NSCLC that had been pretreated with at least one chemotherapeutic regimen and were responding to chemotherapy following 2 to 3 cycles of treatment, entered the trial from May 2004 to February 2006. Patients received gefitinib at an oral dose of 250 mg once daily for 4 weeks.ResultsThirty-three patients were evaluable for response and toxicity. The objective response rate was 24.2% (8 of 33)(95% CI, 11% to 42%). The symptom improvement rate was 54.5% (18 of 33) (95% CI, 41% to 69%). The median duration of response was 7 months (95%CI, 4.0 to 13.2 months). The median time to disease progression (TTP) was 6.5 months (95%CI, 0.7 to 16.6 months). The median overall survival time (OS) was 9.8 months (range, 2.1 to 18.0 months), and the actuarial 1-year survival was 36.4%. Toxicity was relatively mild and included only one patient (3.0%) with grade 4 diarrhea, 1 (3.0%) with grade 3 rash, 1 (3.0%) with grade 3 nausea, and 1 with grade 3 vomiting (3.0%).ConclusionPreliminary results suggest that sequential administration of gefitinib following a response to chemotherapy may be beneficial for Chinese patients with advanced NSCLC. Further randomized clinical trials are needed.
ObjectiveTo evaluate the efficacy, toxicity, and operative complications of docetaxel in combination with S-1 for treating patients with advanced gastric cancer.MethodsFrom July 2013 to December 2014, 30 patients with advanced gastric cancer were treated with i.v. docetaxel 75 mg/m2 on day 1 and oral S-1 60 mg/m2 bid on days 1-14 every 3 weeks. The efficacy and toxicity were evaluated after two chemotherapy cycles.ResultsThe overall treatment response (complete response [CR] + partial response [PR]) was 76.6%(23/30), CR was 6.7% (2/30), PR was 70.0% (21/30), SD was 23.3% (7/30), and progression disease was 0% (0/30). All patients were treated surgically. Twenty-six patients received radical surgery; of them, 23 received D2 lymph node dissection. The other four patients received exploratory celiotomy. No patients died in the group, and the adverse reactions included neutropenia, diarrhea, nausea, and vomiting.ConclusionDocetaxel/S-1 combination is highly active, safe, and well tolerated in patients with advanced gastric cancer. Further investigations in randomized studies are warranted.
Predicting the prognosis of patients in advance is conducive to providing personalized treatment for patients. Our aim was to predict the therapeutic efficacy and progression free survival (PFS) of patients with liver metastasis of colorectal cancer according to the changes of computed tomography (CT) radiomics before and after chemotherapy.MethodsThis retrospective study included 139 patients (397 lesions) with colorectal liver metastases who underwent neoadjuvant chemotherapy from April 2015 to April 2020. We divided the lesions into training cohort and testing cohort with a ratio of 7:3. Two - dimensional region of interest (ROI) was obtained by manually delineating the largest layers of each metastasis lesion. The expanded ROI (3 mm and 5 mm) were also included in the study to characterize microenvironment around tumor. For each of the ROI, 1,316 radiomics features were extracted from delineated plain scan, arterial, and venous phase CT images before and after neoadjuvant chemotherapy. Delta radiomics features were constructed by subtracting the radiomics features after treatment from the radiomics features before treatment. Univariate Cox regression and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression were applied in the training cohort to select the valuable features. Based on clinical characteristics and radiomics features, 7 Cox proportional-hazards model were constructed to predict the PFS of patients. C-index value and Kaplan Meier (KM) analysis were used to evaluate the efficacy of predicting PFS of these models. Moreover, the prediction performance of one-year PFS was also evaluated by area under the curve (AUC).ResultsCompared with the PreRad (Radiomics form pre-treatment CT images; C-index [95% confidence interval (CI)] in testing cohort: 0.614(0.552-0.675) and PostRad models (Radiomics form post-treatment CT images; 0.642(0.578-0.707), the delta model has better PFS prediction performance (Delta radiomics; 0.688(0.627-0.749). By incorporating clinical characteristics, CombDeltaRad obtains the best performance in both training cohort [C-index (95% CI): 0.802(0.772-0.832)] and the testing cohort (0.744(0.686-0.803). For 1-year PFS prediction, CombDeltaRad model obtained the best performance with AUC (95% CI) of 0.871(0.828-0.914) and 0.745 (0.651-0.838) in training cohort and testing cohort, respectively.ConclusionCT radiomics features have the potential to predict PFS in patients with colorectal cancer and liver metastasis who undergo neoadjuvant chemotherapy. By combining pre-treatment radiomics features, post-treatment radiomics features, and clinical characteristics better prediction results can be achieved.
Objective: Biological markers performable in routine practice and able to predict the clinical outcome of advanced non-small cell lung cancer (NSCLC) treated with gefitinib are urgently needed. Methods: We analyzed EGFR / HER2 / HER3 primary tumour immunohistochemical expression in a prospective and consecutive series of 90 Chinese patients. Platinumpretreated patients received a 250 mg oral dose of gefitinib once daily until disease progression; EGFR / HER2 / HER3 tumour status was related with the clinical outcome in terms of response rate (RR), time to disease progression (TTP), and overall survival (OS). Results: A high expression (scores 2-3) of EGFR, HER2 and HER3 was verified in 16.7%, 43.3% and 21.1% of tumors, respectively. EGFR and HER3 status were not significantly related with response, while the HER2 overexpression result was significantly associated with a higher RR (35.9% vs. 15.7%, P = 0.027). The RR in the 13 patients with both HER2 and HER3 expression was also significantly higher than in the other 77 patients (53.8% vs. 22.1%, P = 0.036). EGFR / HER2 / HER3 status was not significantly correlated with TTP or OS. Conclusion: The HER2 immunohistochemical expression can play a role in the clinical management of Chinese patients with advanced NSCLC who are candidates for gefitinib therapy.
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