Case Report: Response to ALK-TKIs in a metastatic lung cancer patient with morphological heterogeneity and consistent molecular features.

Lung adenosquamous carcinoma (ASC) is a rare heterogeneous tumor containing two distinct components of adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). The limited biopsy sampling of the primary tumor might have overlooked either the ADC component or the SQCC component, resulting in a misdiagnosis of pure histology. Genotyping for driver mutations is now routinely performed in clinical settings to identify actionable oncogenic mutations and gene arrangements. Additionally, somatic mutations can potentially serve as a marker of clonal relationships. We report a rare case of ASC lung cancer, in which metastases were identified as ADC, while the primary was initially diagnosed as SQCC based on a fibrobronchoscope brush biopsy. The primary and metastatic tumors shared ALK rearrangement and other mutations support they were derived from a single clone origin. Our hypothesis is that the primary tumor contained a minor component of ADC that was not present in the histologic sections of lung biopsy. After sequential ALK-tyrosine kinase inhibitor (TKI) targeted therapy, both the patient's primary lung tumor and the site of metastatic subcutaneous nodules decreased in size, with the metastatic sites demonstrating more noticeable shrinkage. However, after 11 months of targeted therapy, the patient was found to be resistant to ALK-TKIs. Subsequently, the patient's respiratory status deteriorated rapidly, and a cycle of immunotherapy and chemotherapy did not show efficacy. To the best of our knowledge, this is a very rare case of lung ASC, disseminated metastasizing, with distinct morphology between the primary and metastases. Different therapeutic effects of ALK-TKIs were observed in two different morphological sites, with the metastatic cutaneous lesions shrinking more significantly than the primary lung lesions, though they both harbor the same EML4-ALK rearrangement. This case may provide diagnostic and therapeutic insights into lung ASC.

[Effect of shenfu injection for attenuating the toxicity of cisplatin-based regimens in treating non-small cell lung cancer].

OBJECTIVE: To observe the effect of Shenfu Injection (SFI) for attenuating the toxicity of chemotherapy in treating non-small-cell lung cancer (NSCLC), by the regimens of combined Cisplatin (DDP) with new chemotherapeutic agents, Taxol (TXT), Vinorelbine (NVB) and Gemcitabine (GEM), respectively. METHODS: One hundred and thirty-three patients with NSCLC, who were scheduled to be treated by at least 2 cycles of chemotherapy, with regimen TP (45 cases), NP (42 cases) and GP (46 cases), were enrolled. They were randomized into 2 groups: 67 cases in the SFI pre-treated group and 66 cases in the SFI post-treated group, on them SFI was administered for 10 successive days on the 1st, 2nd, 3rd day of the 1st and the 2nd cycle, respectively. The effects of SFI on toxicity of the three regimens were observed through a self-controlled crossover design. RESULTS: The hemato-toxicity (the toxicity on leukocyte, neutrophil, hemoglobin and platelet) and the digestive toxicity (represented as vomiting, constipation or diarrhea) of chemotherapy revealed in the treated stage (the cycle treated with SFI) were all less than those in the control stage (the cycle untreated with SFI), no matter when SFI was applied, all showed statistical significance (P < 0.05 or P < 0.01). Besides, SFI showed a better toxicity attenuating effect on patients of qi-deficiency and phlegm-dampness type (P < 0.01). CONCLUSION: SFI can relieve the hemato-toxicity and the digestive toxicity of chemotherapy by regimen of combining DDP with TXT, NVB or GEM, and the effect is more significant on patients of qi-deficiency and phlegm-dampness type.

Gefitinib plus Fuzheng Kang'ai Formula () in Patients with Advanced Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. METHODS: A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival (PFS)] and secondary endpoints [median survival time (MST), objective response rate (ORR), disease control rate (DCR) and safety] were observed. RESULTS: No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months (95% CI 3.30-21.69) vs. 8.4 months (95% CI 6.30-10.50; log-rank P<0.01), MST of 21.5 months (95% CI 17.28-25.73) vs. 18.3 months (95% CI 17.97-18.63; log-rank P<0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively (P>0.05). The most common toxic effects in the GF group and G group were rash or acne (42.8% vs. 57.1%, P>0.05), diarrhea (11.5% vs. 31.4%, P<0.05), and stomatitis (2.9% vs. 8.7%, P>0.05). CONCLUSION: Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.

Improvement of quality of life with Shenfu injection in non small cell lung cancer patients treated with gemcitabine plus cisplatin regimen.

OBJECTIVE: To observe the effect of Shenfu injection (SFI) in treating non small cell lung cancer (NSCLC) patients on quality of life with gemcitabine (GEM) plus cisplatin (GP) regimen. METHODS: Thirty-four patients were ready to receive GP regimen chemotherapy for treating NSCLC disease, according to lot-drawing, they were divided into SFI pre-treatment group (18 cases) and SFI post-treatment group (16 cases). SFI pre-treatment group: During the first treatment course, chemotherapy was begun with SFI 60 ml, intravenous dripping on the 3rd day, once daily, consecutively for 10 days; on the 1st day, GP regimen (GEM 1250 mg/m(2), intravenous dripping, on the 1st and 8th day; cisplatin 70 mg/m(2) on the 2nd day; 21 days as one cycle) was carried out; in the second treatment course GP regimen was merely given to serve as the self-control. SFI post-treatment group: the medicament sequence order was reversed from that of pre-treatment group. Using dual international quality of life (QOL) scores, the effect of SFI on the patients' QOL was observed through randomized self pre- and post-crossover control. RESULTS: The QOL in the 34 patients after being treated by SFI in combination with GP chemotherapy regimen in one group, and GP chemotherapy regimen alone in the other, was improved in different degrees, with significant difference (P < 0.01); comparison of SFI combined with GP chemotherapy regimen with GP chemotherapy alone showed that QOL in patients was significantly different (P < 0.01). CONCLUSION: SFI could improve QOL in patients with NSCLC who were treated with GP regimen.

Xiaoji Decoction inhibited cell proliferation and induced apoptosis through Akt signaling pathway in human lung cancer A549 cells.

OBJECTIVE: To investigate the inhibitive effect and the underlying mechanism of Xiaoji Decoction (, XJD) in human lung cancer A549 cells. METHODS: A549 cells in logarithmic proliferation were cultivated in RPMI-1640 containing 10% low, medium or high dosages of XJD serum. The inhibitive effect of XJD in A549 cell proliferation was assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. The pro-apoptotic effect of XJD in A549 cells was observed by fluorescence microscope via Hoechst 33258 staining. The role of the Akt signaling pathway was observed by examining the presence of p-Akt protein by Western blot and the mRNA expression of downstream proteins such as Bcl-2/Bcl-XL-associated death promoter (BAD) and caspase-9 by real time polymerase chain reaction. RESULTS: MTT assay revealed that XJD could inhibit A549 proliferation in a dose- and time-dependent manner. Hoechst 33258 staining showed that XJD induced the typical nuclear apoptotic morphology after XJD treatment. Moreover, XJD could reduce the phosphorylation of Akt and increase the mRNA expression of BAD and caspase-9. CONCLUSIONS: XJD can inhibit the proliferation of A549 cells in a dose- and time-dependent manner through signaling Akt pathway via up-regulating the expression of BAD and caspase-9. XJD may provide a novel therapeutic model for lung cancer and deserve further study.

[Influence of Shenfu Injection on the quality of life of lung cancer patients receiving chemotherapy].

OBJECTIVE: To evaluate the influence of Shenfu Injection (SHF) on the quality of life of patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy. METHODS: A total of 133 patients with NSCLC receiving at least two cycles of chemotherapy with taxol plus cisplatin (TP)/vinorelbine plus cisplatin (NP) or gemcitabine plus cisplatin (GP) were randomized into SHF pre-treatment group (with SHF given only in the first cycle) and SHF post-treatment group (with SHF given only in the second cycle). The Quality of Life Questionnaire-Core 30 (QLQ-C30) and the Functional Living Index-Cancer (FLIC) were used to evaluate the quality of life of the patients after the treatments. RESULTS: Both of the groups showed improved quality of life after the treatments (P<0.01), but the improvements were more obvious in SHF pre-treatment group (P<0.05). SHF showed favorable effects in relieving such adverse effects as fatigue, nausea, vomiting and diarrhea associated with the chemotherapy. CONCLUSION: SHF can improve the quality of life in NSCLC patients receiving chemotherapies.