Amino acid derivative of probenecid potentiates apoptosis-inducing effects of vinblastine by increasing oxidative stress in a cancer cell-specific manner.

Many chemotherapeutic drugs suffer from multidrug resistance (MDR). Efflux transporters, namely ATP-binding cassettes (ABCs), that pump the drugs out of the cancer cells comprise one major reason behind MDR. Therefore, ABC inhibitors have been under development for ages, but unfortunately, without clinical success. In the present study, an l-type amino acid transporter 1 (LAT1)-utilizing derivative of probenecid (PRB) was developed as a cancer cell-targeted efflux inhibitor for P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and/or several multidrug resistant proteins (MRPs), and its ability to increase vinblastine (VBL) cellular accumulation and apoptosis-inducing effects were explored. The novel amino acid derivative of PRB (2) increased the VBL exposure in triple-negative human breast cancer cells (MDA-MB-231) and human glioma cells (U-87MG) by 10-68 -times and 2-5-times, respectively, but not in estrogen receptor-positive human breast cancer cells (MCF-7). However, the combination therapy had greater cytotoxic effects in MCF-7 compared to MDA-MB-231 cells due to the increased oxidative stress recorded in MCF-7 cells. The metabolomic study also revealed that compound 2, together with VBL, decreased the transport of those amino acids essential for the biosynthesis of endogenous anti-oxidant glutathione (GSH). Moreover, the metabolic differences between the outcomes of the studied breast cancer cell lines were explained by the distinct expression profiles of solute carriers (SLCs) that can be concomitantly inhibited. Therefore, attacking several SLCs simultaneously to change the nutrient environment of cancer cells can serve as an adjuvant therapy to other chemotherapeutics, offering an alternative to ABC inhibitors.

Is Radiation Therapy Cost-Effective in the Positron Emission Tomography/Computed Tomography Era for Early-Stage Favorable Hodgkin Lymphoma With Alternative Payment Models?

PURPOSE: Despite multiple randomized trials, variation in practice remains regarding the most effective treatment for early-stage, favorable-risk Hodgkin lymphoma. With increasing emphasis on alternative payment models, we investigate the cost-effectiveness of chemotherapy alone versus combined modality therapy (CMT). METHODS AND MATERIALS: A Markov model was formed to compared 2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) to 2 cycles of ABVD followed by 20 Gy in 10 fractions involved-site radiation therapy. Modalities were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs) and evaluated with a willingness to pay a threshold of $100,000 per QALY gained. RESULTS: The base case analysis showed that CMT is cost-effective compared with ABVD alone, with an incremental cost-effectiveness ratio of $8028 per QALY gained and an incremental cost of $236 gaining 0.029 QALYs. On sensitivity analyses, the results were the most sensitive to changes in recurrence rates. If the recurrence rate differences were ≥6%, CMT was cost-effective. CONCLUSIONS: CMT is a cost-effective strategy for early-stage, favorable-risk Hodgkin lymphoma based on currently available evidence. However, small variations in recurrence-rate estimates dramatically affect strategy cost-effectiveness.

Multicenter analysis of geriatric fitness and real-world outcomes in older patients with classical Hodgkin lymphoma.

We performed a multicenter retrospective analysis across 10 US academic medical centers to evaluate treatment patterns and outcomes in patients age ≥60 years with classic Hodgkin lymphoma (cHL) from 2010-2018. Among 244 eligible patients, median age was 68, 63% had advanced stage (III/IV), 96% had Eastern Cooperative Oncology Group performance status (PS) 0-2, and 12% had documented loss of ≥1 activity of daily living (ADL). Medical comorbidities were assessed by the Cumulative Illness Rating Scale-Geriatric (CIRS-G), where n = 44 (18%) had total scores ≥10. Using multivariable Cox models, only ADL loss predicted shorter progression-free (PFS; hazard ratio [HR] 2.13, P = .007) and overall survival (OS; HR 2.52, P = .02). Most patients (n = 203, 83%) received conventional chemotherapy regimens, including doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; 56%), AVD (14%), and AVD with brentuximab vedotin (BV; 9%). Compared to alternative therapies, conventional regimens significantly improved PFS (HR 0.46, P = .0007) and OS (HR 0.31, P = .0003). Survival was similar following conventional chemotherapy in those ages 60-69 vs ≥70: PFS HR 0.88, P = .63; OS HR 0.73, P = .55. Early treatment discontinuation due to toxicity was more common with CIRS-G ≥10 (28% vs 12%, P = .016) or documented geriatric syndrome (28% vs 13%, P = .02). A competing risk analysis demonstrated improved disease-related survival with conventional therapy (HR 0.29, P = .02) and higher mortality from causes other than disease or treatment with high CIRS-G or geriatric syndromes. This study suggests conventional chemotherapy regimens remain a standard of care in fit older patients with cHL, and highlights the importance of geriatric assessments in defining fitness for cHL therapy going forward.

The patient experience of ABVD treatment in Hodgkin lymphoma: a retrospective cohort study of patient-reported distress.

PURPOSE: Psychological distress is prevalent in Hodgkin lymphoma (HL). Many patients, regardless of prognosis, receive ABVD chemotherapy as first-line treatment, but few studies have specifically examined the nature of distress during this shared treatment experience. METHODS: We conducted a retrospective study of patient-reported distress in HL patients receiving ABVD treatment at a single tertiary care facility. Distress was measured using the National Comprehensive Cancer Network Distress Thermometer and Problem List (PL). We used descriptive statistics and generalized estimating equations to assess the prevalence of distress and specific problem items during treatment and associations with patient- and disease-related factors. RESULTS: We collected data from 50 patients comprising 467 unique encounters, with 369/467 (79.0%) reporting a distress thermometer score. Median distress score was 2 (IQR: 0-5), but actionable distress (distress thermometer ≥4) was noted for 118/369 (32.0%) encounters. Actionable distress was only related to having a prior cancer, which conferred lower odds of actionable distress (OR 0.23, 95% CI 0.07-0.74, p=0.01) Physical and emotional problems were reported for 287/369 (77.8%) and 125/369 (33.9%) visits, respectively. Female patients had greater odds of both physical (OR 3.17, 95% CI 1.32-7.66, p=0.01) and emotional (OR 3.31, 95% CI 1.25-8.73, p=0.02) problems. CONCLUSION: ABVD treatment is associated with a high frequency of actionable distress, with physical and emotional problems acting as primary drivers. Female patients may be particularly vulnerable, while cancer survivors may be uniquely resilient. These findings demonstrate the need to thoroughly screen for and appropriately tailor distress management strategies for HL patients during treatment with ABVD.

[Systemic treatment for management of aggressive fibromatosis in both adult and children: Level of evidence and unsolved questions]. / Traitements systémiques des fibromatoses agressives chez l'adulte et l'enfant : niveau de preuve et questions en suspens.

We summarize here available data about systemic treatments of desmoids tumors, as well in adult patients as pediatric patients. Until 2018, the level of evidence associated with these treatments (NSAI, hormonal therapies, tyrosine kinase inhibitors, chemotherapy) was very low, based on retrospective studies or non-randomized phase 2 trials with limited number of cases. In 2018-2019, 2 large randomized trials have been published, including one large superiority phase 3 trial comparing sorafenib to placebo. This trial clearly demonstrates the clinical benefit of sorafenib over placebo (level of evidence IA). To conclude, wait-and-see policy must be the first-line approach, systemic treatment is indicated in case of disease progression. Randomized trials are feasible in this exceptional disease.

Final Results of the Randomized Phase II NorCap-CA223 Trial Comparing First-Line All-Oral Versus Taxane-Based Chemotherapy for HER2-Negative Metastatic Breast Cancer.

BACKGROUND: The purpose of this study was to evaluate the efficacy of 3 first-line chemotherapy combination regimens for HER2-negative metastatic breast cancer (mBC). PATIENTS AND METHODS: In this open-label, 3-arm, randomized phase II trial, patients were randomized to all-oral NORCAP (vinorelbine/capecitabine), GEMPAC (gemcitabine/paclitaxel), or GEMDOC (gemcitabine/docetaxel) as first-line chemotherapy for HER2-negative mBC. Stratification factors were center, previous (neo)adjuvant anthracycline, and age. The primary end point was disease control rate (DCR; complete or partial response, or stable disease for ≥3 months). RESULTS: The DCR was 73% (95% confidence interval [CI], 59-85) with NORCAP (36 of 49 patients), 78% (95% CI, 64-88) with GEMPAC (39 of 50 patients), and 80% (95% CI, 66-90) with GEMDOC (40 of 50 patients). Objective response rates were 33% (16 of 49 patients), 24% (12 of 50 patients), and 50% (25 of 50 patients), respectively; median progression-free survival was 7.6, 9.0, and 11.4 months, respectively. Median overall survival was 30 to 31 months with all regimens. The most common Grade ≥3 adverse event with each regimen was neutropenia (24 patients [50%], 23 patients [46%], and 43 patients [86%], respectively). The most common nonhematological Grade ≥3 adverse event was fatigue. Grade 2 alopecia occurred in 36 patients (72%) who received GEMPAC and 38 patients (76%) who received GEMDOC, but only 4 patients (8%) who received NORCAP. There was no evidence of a detrimental effect of NORCAP on quality of life. CONCLUSION: All-oral NORCAP is an active first-line chemotherapy regimen and might be offered as an alternative to first-line taxane-based therapy for HER2-negative mBC, particularly if patients wish to avoid alopecia or frequent intravenous administrations.

Efficacy of Aidi Injection () on overexpression of P-glycoprotein induced by vinorelbine and cisplatin regimen in patients with non-small cell lung cancer.

OBJECTIVE: To investigate the efficacy of Aidi Injection () on overexpression of P-glycoprotein (P-gp) induced by vinorelbine and cisplatin (NP) regimen in patients with non-small cell lung cancer (NSCLC), and study the difference between intravenous administration and targeting intratumor administration of Aidi Injection with thoracoscope. METHODS: Totally 150 patients with NSCLC were randomly assigned to the control group, the intravenous group and the intratumor group by the random envelope method, 50 cases in each group. The patients were treated with NP regimen (2 cycles), NP regimen (2 cycles) plus Aidi intravenous injection, or NP regimen (2 cycles) plus Aidi intratumor injection with thoracoscope, respectively for 6 weeks. The clinical effificacy was observed based on Response Evaluation Criteria in Solid Tumors (RECIST) rules, the expression of P-gp in the tumor tissue was tested before, 3 and 6 weeks after treatment, the safety was evaluated by monitoring the toxicity in the process of treatment, and the progression-free survival (PFS) was measured. RESULTS: Fifteen cases dropped out because of the irreconcilable conditions which had no relationship with the treatment, 4 in the control group, 5 in the intravenous group, and 6 in the intratumor group, respectively. Compared with the control group, the response rates (complete remission + partial response) and the disease control rates (complete remission + partial response + stable disease) were significantly higher, the P-gp expressions were significantly decreased after 3 and 6 weeks of treatment, and the Kaplan-Meier survival curves of PFS were significantly longer in the intravenous and intratumor groups (P<0.05 or P<0.01), and the intratumor group showed better effects than the intravenous group (P<0.05 or P<0.01). Compared with the control group, the occurrences of rash, nausea and leukocytopenia were signifificantly decreased in the intravenous and intratumor groups (P<0.05), but without signifificant difference between the intravenous and intratumor groups (P>0.05). CONCLUSION: Aidi Injection not only improves the effificacy of NP regime, but also has the function of reducing adverse events and preventing against overexpression of P-gp induced by chemotherapy of NP regimen.

[Treatment of Radical Resected NSCLC by Chinese Medicine Combined with Adjuvant Chemother- apy: a Clinical Study].

OBJECTIVE: To evaluate the efficacy of Chinese medicine (CM) combined adjuvant chemotherapy in postponing relapse and metastasis of radical resected Ib-IIIa stage non-small cell lung cancer (NSCLC) patients, and to explore its effect in improving their quality of life (QOL) and clinical symptoms. METHODS: We designed a cohort study of 336 radical resected Ib-IIIa NSCLC patients by analyzing disease free survival (DFS) using Log-rank test. They were randomly assigned to the control group (155 cases, treated by adjuvant chemotherapy group) and the test group (181 cases, treated by adjuvant chemotherapy combined CM). By using controlled method, 60 radical resected NSCLC patients undergoing NP/NC program in 2012 (vinorelbine 25 mg/m2, combined with cisplatin 75 mg/m2 on day 1 and day 8/on day 1 or on day 1, 2, and 3; or carboplatin AUC = 5 on day 1) were assigned to the control group (29 cases) and the test group (31 cases). QOL scores (using EORTC QLQ-LC43 questionnaire) and TCM symptoms scores were compared between the two groups before chemotherapy, peri-chemotherapy (one day before the 2nd course of chemotherapy) , and after chemotherapy (20 days after ending the 4th course of chemotherapy). RESULTS: (1) The median DFS was longer in the test group than in the control group, but with no statistical difference between the two groups (42.73 months vs 35.57 months , P = 0.179). In the subgroup analysis, there was statistical difference in IIIa stage DFS. The median IIIa stage DFS of was longer in the test group than in the control group with statistical difference (27.87 months vs 19. 93 months, P = 0.047). (2) In the control study, repeated measured data indicated there was significant difference in physical functions between the two groups (P < 0.05). Total scores for health states decreased more in the test group than in the control group, but with no statistical difference (P > 0.05). Scores for constipation and CM syndrome scores were higher in the test group than in the control group (P < 0.05). CONCLUSIONS: CM had advantages in postponing DFS of radical resected NSCLC patients, especially in IIIa stage. CM could improve their QOL and clinical symptoms during adjuvant chemotherapy.

Singapore Cancer Network (SCAN) Guidelines for Neoadjuvant and Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer.

INTRODUCTION: The SCAN genitourinary cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. RESULTS: Three international guidelines were evaluated- those developed by the National Comprehensive Cancer Network (2014), the European Society of Medical Oncology (2011) and the European Association of Urology (2013). Recommendations on the use of neoadjuvant and adjuvant chemotherapy in MIBC were developed. CONCLUSION: These adapted guidelines form the SCAN Guidelines 2015 for neoadjuvant and adjuvant chemotherapy in MIBC.

[Radiotherapy plus concomitant systemic therapies for patients with brain metastases from breast cancer]. / Place de l'association radiothérapie encéphalique et thérapies systémiques dans le traitement des métastases cérébrales d'un cancer du sein.

The incidence of brain metastases from breast cancer is increasing with diagnosis and therapeutics progress, especially with systemic therapies. The occurrence of multiple brain metastases remains a delicate situation when surgery and stereotactic radiosurgery are not indicated, nor available. Treatment strategy is based on the patient's general condition and extracranial disease status. Whole brain radiation therapy remains the gold standard local treatment but its efficacy is limited with a median overall survival of 6 months. New strategies are needed for increasing survival and patients' quality of life. Combining radiation therapy and chemotherapy has been a subject of interest. This article sums up the different radiotherapy plus concomitant systemic therapies combinations for the treatment of brain metastases from breast cancer.

Chemotherapeutic and targeted biological agents for metastatic bladder cancer: a comprehensive review.

The American Cancer Society estimates that 73 510 new cases of bladder cancer will be diagnosed and 15 000 deaths will result this year. The paper summarizes the clinical evidence for the use of platinum-based, non-platinum-based and new targeted biological agents, while reporting the future directions in the treatment of metastatic bladder cancer. For cisplatin-base regimens, the combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) has been the mainstream treatment for both advanced and metastatic bladder cancers. It showed significant improvement in the complete response rate and overall survival time in comparison with single-agent cisplatin. For cisplatin-ineligible patients, namely patients with renal impairment, symptomatic cardiac disease and poor performance status, alternative therapies consisting of paclitaxel, gemcitabine and carboplatin were shown to be of benefit. Pemetrexed and vinflunine have also shown effectiveness, with small but demonstrable overall survival benefits. Gemcitabine-based doublet therapies (combined with paclitaxel, docetaxel, irinotecan, oxaliplatin or epirubicin) have all been shown to be effective and well-tolerated. Several new targeted therapies, such as gefetinib, sorafenib and lapatinib, have received attention in recent years; however, their effectiveness as single agents in a relapse setting have not been optimal and more studies are warranted.

Effects of Jianpi Jiedu Recipe on reversion of P-glycoprotein-mediated multidrug resistance through COX-2 pathway in colorectal cancer.

OBJECTIVE: To evaluate the underlying mechanism of Jianpi Jiedu Recipe (, JJR) in the reversion of multidrug resistance concerning colorectal cancer in vitro and in vivo. METHODS: Mice were treated orally with JJR at a daily 4.25 g/(kg·day) or injected with vinblastine (VCR) 2.5 mg/(kg·day) for 3 weeks after having been inoculated with HCT8/V cells; tumor tissues were assayed by hematoxylin and eosin staining. Firstly, the effects of JJR on the expression of cyclooxygenase-2 (COX-2) were tested by real-time polymerase chain reaction (PCR) technique and COX-2 gene silenced by siRNA. Secondly, the variation of intracellular concentration of oxaliplatin (L-OHP) was evaluated by the inductively coupled plasma mass spectroscopy (ICPMS) in HCT8/V and its COX-2 siRNA cells; the concentration of JJR combined with chemotherapeutic drugs and the reverse effect of multidrug resistance (MDR) in HCT8/V cells was evaluated by the MTT assay. Thirdly, real-time quantitative PCR and Western blot analysis were used to detect the multidrug resistance gene 1 (MDR1) mRNA and P-gp expression. RESULTS: JJR had an inhibitory effect on the growth of tumors in vivo, and it, in combination with chemotherapeutic drugs, could reverse the drug-resistance of HCT8/V cells and increase the sensitivity of HCT8/V cells to VCR, DDP, 5-Fu, and THP. ICP-MS results showed that JJR could increase the concentration of drugs in HCT8/V cells (P<0.01). Furthermore, it was shown that JJR could reverse drug resistance of colorectal cancer cells by decreasing MDR1 expression and P-gp level via downregulation of COX-2, which has been represented as one of the major mechanisms that contributes to the MDR phenotype (P<0.01). CONCLUSION: JJR reversed multidrug resistance and enhanced the sensitivity to chemotherapy, which could be attributed to the down-regulation of COX-2 in MDR1/P-gp-mediated MDR colorectal cancer after chemotherapy.

[Chemotherapy in male external genital organs (testicular and penile cancer)]. / Chimiothérapie des organes génitaux externes chez l'homme (cancer du testicule et du pénis).

AIM: To describe drugs used in the chemotherapy of testis and penis neoplasms. MATERIAL: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned. RESULTS: Nowadays, the chemotherapy is perfectly codified in adjuvant treatment or in first-line treatment of metastatic testis cancer. A single dose of carboplatin for seminoma testicular (stage I) in adjuvant treatment situation is one of the latest advances. Concerning penis cancer, the optimal protocols validated by a high level of evidence are missing. CONCLUSION: The chemotherapy in testis and penis neoplasms knew few advances in recent years. So, it is necessary to include patients in clinical research protocols.

Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models.

ETHNOPHARMACOLOGICAL RELEVANCE: Catharanthus roseus (L). Don (Catharanthus roseus) is a traditional anti-diabetic herb widely used in many countries, and the alkaloids of Catharanthus roseus are considered to possess hypoglycemic ability. AIM OF THE STUDY: To systematically investigate the potential anti-diabetic effects and the underlying anti-diabetic mechanisms of vindoline, one of the alkaloids in Catharanthus roseus. MATERIALS AND METHODS: The regulation of vindoline against the glucose-stimulated insulin secretion (GSIS) was examined in insulinoma MIN6 cells and primary pancreatic islets. Insulin concentration was detected by Elisa assay. Diabetic models of db/db mice and type 2 diabetic rats induced by high-fat diet combining with streptozotocin (STZ/HFD-induced type 2 diabetic rats) were used to evaluate the anti-diabetic effect of vindoline in vivo. Daily oral treatment with vindoline (20mg/kg) to diabetic mice/rats for 4 weeks, body weight and blood glucose were determined every week, oral glucose tolerance test (OGTT) was performed after 4 weeks. RESULTS: Vindoline enhanced GSIS in both glucose- and dose-dependent manners (EC50 = 50 µM). It was determined that vindoline acted as a Kv2.1 inhibitor able to reduce the voltage-dependent outward potassium currents finally enhancing insulin secretion. It protected ß-cells from the cytokines-induced apoptosis following its inhibitory role in Kv2.1. Moreover, vindoline (20mg/kg) treatment significantly improved glucose homeostasis in db/db mice and STZ/HFD-induced type 2 diabetic rats, as reflected by its functions in increasing plasma insulin concentration, protecting the pancreatic ß-cells from damage, decreasing fasting blood glucose and glycated hemoglobin (HbA1c), improving OGTT and reducing plasma triglyceride (TG). CONCLUSION: Our findings suggested that vindoline might contribute to the anti-diabetic effects of Catharanthus roseus, and this natural product may find its more applications in the improvement of ß-cell dysfunction and further the potential treatment of type 2 diabetes.

An autocrine loop between TGF-ß1 and the transcription factor brachyury controls the transition of human carcinoma cells into a mesenchymal phenotype.

The epithelial-mesenchymal transition (EMT) is a process associated with the metastasis of solid tumors as well as with the acquisition of resistance to standard anticancer modalities. A major initiator of EMT in carcinoma cells is TGF-ß, which has been shown to induce the expression of several transcription factors ultimately responsible for initiating and maintaining the EMT program. We have previously identified Brachyury, a T-box transcription factor, as an inducer of mesenchymal features in human carcinoma cells. In this study, a potential link between Brachyury and TGF-ß signaling has been investigated. The results show for the first time that Brachyury expression is enhanced during TGF-ß1-induced EMT in various human cancer cell lines, and that a positive feedback loop is established between Brachyury and TGF-ß1 in mesenchymal-like tumor cells. In this context, Brachyury overexpression is shown to promote upregulation of TGF-ß1 at the mRNA and protein levels, an effect mediated by activation of the TGF-ß1 promoter in the presence of high levels of Brachyury. Furthermore, inhibition of TGF-ß1 signaling by a small-molecule inhibitor of TGF-ß receptor type I decreases Brachyury expression, induces a mesenchymal-to-epithelial transition, and renders cancer cells more susceptible to chemotherapy. This study thus has implications for the future development of clinical trials using TGF-ß inhibitors in combination with other anticancer agents.

A systematic review of vinorelbine for the treatment of breast cancer.

The purpose of this study was to investigate the efficacy and safety profile of vinorelbine-based chemotherapy in different settings for the treatment of breast cancer. We performed a computerized search using combinations of the following keywords: "breast cancer", "breast neoplasms", "trial", "vinorelbine" and "navelbine". A total of 20 trials were included in this analysis, with a total of 5,080 patients accrued. Taxane was associated with enhanced overall survival (OS; p = 0.027) and response rate (RR; p = 0.037) as compared with vinorelbine in monotherapy, but did not show significantly favored progression-free survival (PFS; p = 0.136). Vinorelbine alone was equivalent to fluoropyrimidine treatment in RR (p = 0.79) for the treatment of metastatic breast cancer. For vinorelbine-combined regimens, the analysis showed that the vinorelbine group gave similar results as other regimens for OS (p = 0.849) and PFS (p = 0.143). The RR of vinorelbine-combined regimens was slightly better than that of the other regimens (OR, 1.17), but the difference was not statistically significant. In neoadjuvant setting, vinorelbine treatment was as active as AC (doxorubicin, cyclophosphamide) or DAC (doxorubicin, cyclophosphamide, docetaxel) regimens with respect to RR (p = 0.76) and pathologic complete response (pCR; p = 0.77), but showed lower occurrence of grade 3/4 adverse effects. The analysis also demonstrated that vinorelbine-containing therapy is effective as adjuvant, front-line or salvage therapy of metastatic breast cancer, even for patients who were previously treated with anthracyclines or taxanes.

[Effects of chemotherapy combined with Chinese herbal medicine Kangliu Zengxiao decoction on tumor markers of patients with advanced non-small-cell lung cancer: a randomized, controlled trial].

BACKGROUND: Tumor markers are widely used in clinical practice and have become important indicators in assessing cancer progress. There is increasing concern that chemotherapy combined with traditional Chinese medicine has effects in decreasing the level of tumor markers. OBJECTIVE: To investigate the effects of chemotherapy combined with Kangliu Zengxiao Decoction (KLZX), a compound Chinese herbal drug, on tumor markers carbohydrate antigen 50 (CA 50), cytokeratin 19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) in patients with advanced non-small-cell lung cancer (NSCLC) and to explore the relationships between clinical efficacy and tumor markers. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Patients were included from Punan Hospital of Shanghai Pudong New District and Longhua Hospital between October 2008 and December 2009. Seventy-four subjects with advanced NSCLC were randomly assigned into treatment group (n=37) and control group (n=37). Patients in the control group were treated with chemotherapy alone while patients in the treatment group were treated with chemotherapy combined with KLZX. Chemotherapy of NP (vinorelbine + cisplatin) was given for two cycles and patients in the treatment group were administered with KLZX during chemotherapy. MAIN OUTCOME MEASURES: Levels of CA50, CYFRA21-1 and CEA before and after treatment were evaluated and the relationship between changes in levels of tumor makers and tumor size, clinical symptoms and living condition score (Karnofsky score) was analyzed. RESULTS: No patients achieved a complete remission. The disease control rates (complete remission (CR)+partial remission (PR)+no change (NC)) were 89.20% (33/37) and 70.30% (26/37) in the treatment and control group respectively (P<0.05). The levels of CA50, CYFRA21-1 and CEA were clearly decreased in the treatment group after treatment (P<0.05) while also decreased in the patients without progression of disease. There were no obvious changes of CA50, CYFRA21-1 and CEA in the control group, and there was even a trend of increase. Furthermore, the improvement rates of clinical syndrome were 51% (19/37) vs 11% (4/37) (P<0.05) in the treatment group and control group respectively. The total response rates of quality of life were 91.89% (34/37) vs 56.76% (21/37) (P<0.01) in the treatment and control group respectively. CONCLUSION: Combined chemotherapy with KLZX in treating advanced NSCLC can acquire better stabilizing tumor foci, decrease levels of tumor markers and improve the clinical symptoms and Karnofsky score.

Vinflunine: drug safety evaluation of this novel synthetic vinca alkaloid.

INTRODUCTION: Vinca alkaloid agents have been widely used in several different types of malignancies. However, cancer cells, ultimately, develop resistance to these agents. Therefore, the development of new agents with improved efficacy is warranted. Recently, a new synthetic vinca alkaloid, vinflunine, was developed through the addition of two fluor molecules by superacidic chemistry. AREAS COVERED: The authors describe the development of the new vinca alkaloid vinflunine from preclinical studies to the late-stage clinical trials, highlighting the most important clinical and safety data of vinflunine. In vitro and in vivo studies have shown a superior efficacy of vinflunine over other vinca alkaloids and with an improved safety profile. Early clinical trials have demonstrated a significant activity of vinflunine against different malignancies. Phase III trials showed that vinflunine increases survival in patients with advanced transitional cell carcinoma of the urothelium (TCCU) tract treated in the second-line and is as effective as docetaxel in second-line NSCLC. EXPERT OPINION: Vinflunine is currently approved in Europe for the treatment of second-line TCCU and is currently being developed in other malignancies. It has been shown to have predictable and manageable adverse effects, such as neutropenia, anemia, constipation and fatigue.

Traditional Chinese medicine herbal treatment may have a relevant impact on the prognosis of patients with stage IV adenocarcinoma of the lung treated with platinum-based chemotherapy or combined targeted therapy and chemotherapy.

BACKGROUND: Targeted therapy (TT), chemotherapy, and traditional Chinese medicine herbal treatment (TCM) can improve the prognosis of advanced pulmonary adenocarcinoma patients. Their independent prognostic value is unknown. OBJECTIVE: To study whether TCM improves survival in stage IV pulmonary adenocarcinoma patients with platinum-based chemotherapy (PBT), or combined PBT and second-line TT. METHODS: Retrospective analysis of 133 fully ambulant clinical outpatients treated with PBT alone or PBT with/without second-line TT, with/without TCM. Univariate (Kaplan-Meier) and multivariable (Cox model) survival analysis were performed, using disease-specific mortality as an endpoint. RESULTS: Gender (P = .002), TT (P < .0001), and TCM (P < .0001) had univariate prognostic value but not age, radiotherapy, or TCM syndrome differentiation (P > .10). TCM herbal treatment (P < .0001) and TT (P = .03) had multivariable independent prognostic value. TCM-treated patients (n = 103, PBT+TT+TCM+ = 62; PBT+TT-TCM+ =41) had 88% 1-year overall survival rate with median survival time (MST) of 27 months, contrasting 27% 1-year overall survival and MST of 5.0 months for non-TCM-treated (n = 30) patients. Patients with chemotherapy/TT/TCM (PBT+TT+TCM+, n = 62), TCM without TT (PBT+TT-TCM+, n = 41), or chemotherapy only (PBT+TT-TCM-, n = 30), had 1-year survival rates of 94%, 78%, and 27% respectively; for these 3 groups, respectively, MST was not reached (MST of 30.9 months), 22.6, and 5.0 months (P < .0001). CONCLUSIONS: TCM herbal treatment may improve survival of stage IV pulmonary adenocarcinoma patients treated with chemotherapy without or with second-line TT. This warrants formal phase 1 and 2 trials and ultimately properly designed prospective clinical validation trials with adequate methodology developed for data collection.

Combination of oral vinorelbine and capecitabine in the treatment of metastatic breast cancer patients previously exposed to anthracyclines: a pilot study.

BACKGROUND AND OBJECTIVES: Vinorelbine and capecitabine are both active in breast cancer with moderate toxicity. DESIGN AND SETTING: A pilot study conducted from December 2007 to January 2010 in patients with metastatic breast cancer (MBC) to evaluate efficacy and safety. PATIENTS AND METHODS: The study included patients with MBC who were previously treated by anthracyclines either during the adjuvant phase or the metastatic phase. Patients were treated with oral vinorelbine (60 mg/m2) on day 1+8 and capecitabine (1000 mg/m2) twice daily (VC) from day 1 to day 14 with both repeated every 3 weeks until progression, refusal or for a maximum of 8 cycles. A dose reduction was made in case of grade 3 and 4 toxicities. RESULTS: Of 31 women (median age, 51 years), 12 cases were first-line therapy and 19 cases were second-line therapy or greater, and 30 were evaluable for response. Two patients (6.4%) achieved complete response and 15 patients (48.4%) had a partial response giving an overall response rate of 54.8% (95% CI, 42%-68%). Time- to-disease progression was 7.8 months for patients receiving VC as first-line therapy versus 6 months for patients receiving VC as second-line therapy or more, while median survival time was 22 months and 10 months for the two groups, respectively. CONCLUSIONS: The oral VC regimen is effective and safe in patients with MBC previously exposed to anthracyclines, and offers a promising alternative to the intravenous route. Its role as a salvage therapy following anthracycline failure or as first-line chemotherapy requires further studies.