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1.
Ibrahim Yildiz Faruk Tas Leyla Kilic Fatma Sen Pinar Saip Yesim Eralp Serkan Keskin Senem Karabulut Rumeysa Ciftci Murat Serilmez Vildan Yasasever Adnan Aydiner 《Cancer chemotherapy and pharmacology》2013,72(2):437-444
Purpose
This study was conducted to determine the clinical significance of serum M30 and M65 in epithelial ovarian cancer (EOC).Methods
A total of 56 patients with EOC and 56 healthy women were included in the study. All of the patients received platinum-based chemotherapy. Pretreatment levels of M30 and M65 were measured using the quantitative ELISA method.Results
The median M30 and M65 serum levels were significantly elevated in the EOC patients compared with the healthy controls (96.7 vs. 69.5, p = 0.028 and 436.4 versus 166.3, p < 0.001, respectively). The cut-off value of 423.4 U/L for M65 determined with ROC analysis, predicted progression with 75.1 % sensitivity and 65.6 % specificity (AUC = 0.708, p = 0.008). Patients with higher M65 levels had shorter progression-free survival (PFS) (p = 0.021). Both M30 and M65 serum levels were significantly higher for serous-type histology (p = 0.001 and p < 0.001, respectively). Increased M65 serum levels were associated with advanced disease (p = 0.005) and higher grade (p = 0.005). Moreover, M65 levels were higher for chemotherapy-resistant patients (p = 0.04). Multivariate analysis revealed that an elevated serum M65 level was the only significant independent prognostic factor (p = 0.039, HR 3.792).Conclusions
These results indicated that serum M30 and M65 levels were significantly elevated in patients with EOC compared with healthy women. Particularly, high serum M65 levels were associated with poor prognosis and resistance to platinum-based chemotherapy. 相似文献2.
John Rinehart Susanne Arnold Goetz Kloecker Allen Lim Muhammad-Ali Zaydan Thomas Baeker Jewraj G. Maheshwari Harry Carloss Stacey Slone Brent Shelton Jessica Croley Elizabeth Kvale Michael Brooks Mark Leggas 《Cancer chemotherapy and pharmacology》2013,71(5):1375-1383
Purpose
Pre-clinical and early-phase clinical studies have demonstrated that dexamethasone (DEX) administration prior to chemotherapy reduces toxicity and enhances efficacy in the treatment of cancer. We undertook a randomized, phase II multi-institutional trial to evaluate these effects in patients with Stage IV non-small cell lung cancer.Methods
Patients were treated with carboplatin on day 1 and gemcitabine on days 1 and 8 every 21 days, for up to 6 cycles. Patients were randomized not to receive (Arm 1, n = 25) or to receive (Arm 2, n = 31) DEX orally for 4 days prior to chemotherapy on days 1 and 8. The primary endpoint was the incidence/course of grade 3 and 4 hematologic toxicity. Secondary endpoints included efficacy [response and overall survival (OS)] and evaluation of the Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin levels, to predict survival and toxicity.Results
The incidence/course of grade 3 and 4 hematologic toxicity was significantly reduced in Arm 2 (DEX) versus Arm 1 (no DEX): neutrophils = 13 versus 40 % (p = 0.009) and platelets = 23 versus 44 % (p = 0.03). Response rates and OS were higher in Arm 2 versus Arm 1: 8/31 versus 2/25 (partial response, p = ns) and 378 versus 291 days (p = ns). The GPS significantly predicted survival OS (p = 0.04) but not toxicity.Conclusions
Pre-treating patients with DEX is a safe, effective, and economic method of reducing the hematologic toxicity of carboplatin and gemcitabine. Our data suggest efficacy may also be enhanced by DEX pre-treatment. 相似文献3.
Takaaki Tokito Takehito Shukuya Hiroaki Akamatsu Tetsuhiko Taira Akira Ono Hirotsugu Kenmotsu Tateaki Naito Haruyasu Murakami Toshiaki Takahashi Masahiro Endo Nobuyuki Yamamoto 《Cancer chemotherapy and pharmacology》2013,71(6):1493-1498
Purpose
Skeletal-related events (SREs) negatively affect the quality of life of patients with cancer. Vascular endothelial growth factor receptor (VEGFR)-targeted therapy is effective against bone metastasis in animal models, but the clinical efficacy of anti-VEGFR inhibitors against bone metastases remains unclear. Therefore, we aimed to investigate the efficacy of chemotherapy with bevacizumab, an anti-VEGF antibody, against bone metastases.Methods
We retrospectively reviewed consecutive patients with non-squamous non-small cell lung cancer who received first-line platinum-based chemotherapy with zoledronic acid at Shizuoka Cancer Center between 2007 and 2011.Results
Of 25 patients, 13 received bevacizumab-based chemotherapy (BEV group) and 12 received chemotherapy without bevacizumab (non-BEV group). The overall response (54 vs. 8 %, p = 0.01) and disease control (100 vs. 50 %, p = 0.01) rates were higher in the BEV group than in the non-BEV group. The bone-specific response (23 vs. 0 %, p = 0.038) and disease control (100 vs. 67 %, p = 0.01) rates were also higher in the BEV group. The median time to progression (TTP) for bone metastases was higher in the BEV group (13.7 vs. 4.3 months, p = 0.06), whereas that for overall disease was similar between the groups (5.7 vs. 2.6 months, p = 0.17). The proportions of patients with SREs were 23 and 50 % in the BEV and non-BEV groups, respectively (p = 0.16).Conclusion
Bevacizumab might potentiate the antitumor activity of chemotherapy against systemic disease and bone metastases, prolonging bone-specific TTP and reducing the incidence of SRE. 相似文献4.
M. Bendle J. Pealing P. Papanastasopoulos M. Bower 《Cancer chemotherapy and pharmacology》2014,74(3):611-615
Purpose
People living with HIV (PLWH) are at increased risk of cancer, both non-AIDS- and AIDS-defining malignancies (NADM and ADM). Systemic chemotherapy also predisposes to secondary cancers. The potential contribution of systemic liposomal anthracycline chemotherapy (SLAC) to the development of second cancers in PLWH is unknown.Methods
Since 1998, we have treated 495 PLWH and Kaposi’s sarcoma (KS) with a stage-stratified approach including 163 who received SLAC as first-line treatment for KS. Subsequent ADM and NADM diagnosed in this population were recorded.Results
More patients who received SLAC had T1 stage disease (p < 0.0001) and lower CD4 cell counts (p < 0.0001) in line with the stage-stratified treatment, but there were no significant differences in age (p = 0.29), gender (p = 0.18), prior AIDS-defining illness (p = 0.45), plasma HIV viral load (p = 0.15), or HHV8 viral load (p = 0.39) between the two groups. During a median follow-up of 4.6 years (maximum 15 years) from KS diagnosis, 28 patients developed a second cancer (5 ADM and 23 NADM). The 5-year cumulative risk of second cancer is 5.8 % (95 % CI 3.0–8.6 %), and there is no significant difference in the rate between those treated with SLAC and those not (log rank p = 0.19). Most patients (n = 131) were treated with daunoxome (liposomal daunorubicin) chemotherapy, and there was no significant correlation between risk of second cancer and cumulative dose of daunoxome (p = 0.23).Conclusion
Although the risk of second cancer after a diagnosis of KS in PLWH is high, systemic liposomal anthracycline chemotherapy does not appear to increase the risk. 相似文献5.
Gakuji Osawa Kazuhiko Yoshimatsu Hajime Yokomizo Sachiyo Okayama Masano Sagawa Yoshihiko Naritaka 《Cancer chemotherapy and pharmacology》2013,72(1):209-215
Purpose
The imaging factor predicting the response to bevacizumab (BV) as concomitant chemotherapy has yet to be determined. This study examined correlation between response to chemotherapy with concomitant BV for hepatic metastasis of colorectal cancer and degree of contrast enhancement (CE) using contrast-enhanced computed tomography (CT).Methods
Data were analyzed retrospectively for 35 patients treated with oxaliplatin-based chemotherapy as the first-line chemotherapy. Patient data were divided according to treatment with concomitant BV (BV group: n = 20, non-BV group: n = 15). Using an image control system, the degree of CE was evaluated by the ratio of the contrast-enhanced CT value of hepatic metastatic lesions to plain CT value, whereby patients were classified into the high-CE and low-CE group.Results
After completion of chemotherapy treatment, the degree of enhancement of hepatic metastasis in the BV group was significantly lower than that in the non-BV group (p = 0.03). In the BV group, a significant correlation between higher contrast enhancement and higher tumor shrinkage rate was observed (R 2 = 0.25, p = 0.03), whereas no such correlation was noted in the non-BV group. In the high-CE group (n = 18), the tumor shrinkage rate increased to 29.6 % in the BV group compared with ?1.46 % in the non-BV group (p = 0.03), whereas in the low-CE group, no significant difference was noted between patients in the two groups.Conclusion
Pretreatment evaluation of the degree of CE correlated with the response to concomitant chemotherapy with BV. 相似文献6.
Faruk Tas Senem Karabulut Murat Serilmez Rumeysa Ciftci Derya Duranyildiz 《Cancer chemotherapy and pharmacology》2014,73(3):631-637
Purpose
Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of multiple malignancies, and its expression also strongly affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of EGFR in epithelial ovarian cancer (EOC) patients.Materials and methods
A total of 50 patients with a pathologically confirmed diagnosis of EOC were enrolled into this study. Serum EGFR levels were determined by the solid-phase sandwich ELISA method. Age and sex matched 20 healthy controls were included in the analysis.Results
Median age of patients was 56.5 years old, range 22–83 years. Majority of the patients had advanced disease (FIGO stage III-IV) (90 %). No significant difference in baseline serum EGFR levels between EOC patients and controls (65.9 vs. 65.4 ng/mL, p = 0.86). Patients with normal CA 125 had higher serum EGFR level compared with the higher CA 125 level (p = 0.02). No other clinical variables including histology, stage of disease, and response to chemotherapy were found to be correlated with serum EGFR assay (p > 0.05). The patients with increased serum EGFR levels had poor progression-free survival than those with lower levels (median survival 4 vs. 12 months, respectively, p = 0.01). However, serum EGFR level was found no prognostic role for overall survival (p = 0.15).Conclusion
Increased serum level of EGFR is associated with poor progression-free survival in EOC patients. 相似文献7.
Objective
This retrospective analysis evaluates the clinical outcomes of extensive-stage small cell lung cancer (SCLC) patients who received second-line chemotherapy after platinum-based first-line chemotherapy, especially focusing on efficacy and toxicity between single-agent and combination chemotherapy.Methods
We retrospectively reviewed 193 patients who received second-line chemotherapy for extensive-stage SCLC. Patients relapsing or progressing beyond 90 days were defined as sensitive recurrence patients, and below 90 days as refractory recurrence patients. Survival curves were plotted using the Kaplan–Meier method. The Cox proportional hazard model was used for multivariate analysis.Results
138 patients received combination chemotherapy and 55 received single-agent treatment. The objective response rate (ORR) was 25.4 % in the combination group and 9.1 % in the single-agent group (p = 0.012). The disease control rate (DCR) was 65.2 and 34.5 %, respectively, (p < 0.001). The progression-free survival (PFS) was 3.80 months in the combination group and 2.13 months in the single-agent group (p = 0.001). In the sensitive recurrence group, the median PFS was 3.80 months in combination group and 3.23 months in single-agent group (p = 0.092). In the refractory recurrence group, the median PFS was 2.83 and 1.30 months, respectively (p = 0.001). The grade III/IV toxicity in single-agent group is much lower than the combination group (56.4 vs. 74.6 %, p = 0.013).Conclusion
Our retrospective data suggest a potential role of prolonging the PFS for combination treatment in extensive-stage SCLC second-line treatment, especially for the refractory recurrence patients, but with more toxicity as compared to single-agent. 相似文献8.
Oscar Arrieta Luis-Alberto Medina Enrique Estrada-Lobato Laura-Alejandra Ramírez-Tirado Víctor-Osvaldo Mendoza-García Jaime de la Garza-Salazar 《Cancer chemotherapy and pharmacology》2014,74(1):211-215
Background
There are currently no available biomarkers for advanced pleural mesothelioma that determine which patients could benefit from a specific chemotherapy regimen.Methods
Based on the results of a previously published phase II study, we associated the 99mTechnetium-labelled liposomal doxorubicin (99mTc-LD) uptake value (75 % cut-off) with the response rate, progression-free survival and overall survival of patients treated with a combination of liposomal doxorubicin and cisplatin.Results
Patients with tumours exhibiting increased 99mTc-LD uptake showed better response rates, progression-free survival and overall survival than those exhibiting lower uptake 73.3 versus 15 % (p < 0.001); 6.9 versus 3.2 months (p = 0.033) and 23 versus 6.6 months (p = 0.001), respectively.Conclusion
99mTc-DL uptake in tumour tissue could define a set of patients who would benefit from this chemotherapy regimen. 相似文献9.
Changhoon Yoo Mi Ra Yun Jin-Hee Ahn Kyung Hae Jung Hwa Jung Kim Jeong Eun Kim Jeong Yun Park Kwang Ok Park Dok Hyun Yoon Sung-Bae Kim 《Cancer chemotherapy and pharmacology》2013,72(3):565-575
Purpose
We conducted a prospective observational study for premenopausal women receiving adjuvant adriamycin and cyclophosphamide-containing regimens to define the pattern of chemotherapy-induced amenorrhea (CIA), the menopause-specific quality of life (MENQOL), and the hormone profiles.Methods
From October 2003 to July 2007, 387 patients with breast cancer who underwent curative surgery were prospectively included. Patient self-assessment by MENQOL questionnaires and blood samples for hormone assays were taken before chemotherapy, and 1, 6, and 12 months after chemotherapy was completed.Results
Patients were categorized into three groups according to their duration and reversibility of amenorrhea, with 312 eligible patients split into long-term CIA (n = 180, 57.7 %), temporary CIA (n = 113, 36.2 %), and menstrual irregularity (n = 19, 6.1 %) groups. Risk factors for long-term CIA were identified as age ≥40 years (p < 0.001), the addition of taxane (p = 0.01), and tamoxifen use (p = 0.03). MENQOL was worst immediately after the completion of adjuvant chemotherapy, and this was not fully recovered even 12 months after chemotherapy had finished. Age ≥40 years and tamoxifen exposure were inversely associated with MENQOL. In long-term CIA patients, the level of follicle-stimulating hormone increased after chemotherapy; this level, however, was reduced in patients who received tamoxifen, but remained high and stable in those who did not (p < 0.001 at 6 months; p < 0.001 at 12 months).Conclusion
This study showed that most premenopausal breast cancer patients who received adjuvant chemotherapy experienced clinically significant CIA, followed by impaired MENQOL. Our findings may be relevant in the decision-making processes for premenopausal women with breast cancer. 相似文献10.
Ji-Won Kim Jee Hyun Kim Seock-Ah Im Kyung-Hun Lee Jin-Soo Kim Tae-Yong Kim Sae-Won Han Yoon Kyung Jeon Do-Youn Oh Tae-You Kim In Ae Park 《Cancer chemotherapy and pharmacology》2013,72(5):1023-1029
Purpose
Epidermal growth factor (EGF) is a ligand for the epidermal growth factor receptor (EGFR). Human epidermal growth factor receptor 2 (HER2) shares common signal pathways and forms a heterodimer with EGFR. In this study, we investigated the clinical and pathologic implications of serum EGF levels in patients with HER2-positive metastatic breast cancer (MBC).Methods
We analyzed serum EGF levels from baseline serum samples of consecutive patients with HER2-positive MBC who received first-line trastuzumab plus taxane chemotherapy and correlated them with treatment outcomes and pathologic features.Results
A total of 50 women were analyzed. The median age was 47 years (range 27–72 years). Patients with high serum EGF levels (≥10.0 pg/mL) had significantly longer overall survival (47.0 months (95 % confidence interval (CI) 28.3–65.7 months) vs. 23.3 months (95 % CI 13.5–33.1 months); p = 0.009) with a tendency toward longer progression-free survival (p = 0.123). Serum EGF levels were not associated with hematologic or cardiac adverse events. Progesterone receptor-positive patients had significantly higher serum EGF levels than progesterone receptor-negative patients (24.3 pg/mL (range 9.5–69.0 pg/mL) vs. 12.3 pg/mL (range 0.0–59.5 pg/mL); p = 0.006).Conclusions
Our data suggest that high serum EGF levels may be associated with good prognosis in patients with HER2-positive MBC receiving trastuzumab plus taxane chemotherapy. In addition, serum EGF levels were associated with progesterone receptor positivity. 相似文献11.
Faruk Tas Senem Karabulut Rumeysa Ciftci Fatma Sen Burak Sakar Rian Disci Derya Duranyildiz 《Cancer chemotherapy and pharmacology》2014,73(6):1163-1171
Purpose
Serum LDH, CEA, and CA19-9 levels are important tumor markers in pancreatic cancer. The purpose of this study was to evaluate the clinical significance of serum LDH, CEA, and CA19-9 levels in metastatic pancreatic cancer (MPC) receiving gemcitabine-based chemotherapy.Materials and methods
In this retrospective study, we analyzed the outcome of 196 MPC patients who are treated with gemcitabine-based chemotherapy in our clinic.Results
Positivity rates of serum LDH, CEA, and CA19-9 were 22, 40, and 83 %, respectively. Likewise, the rates of very high serum levels of tumor markers were correlated with these positivity rates (9 % for LDH, 30 % for CEA, and 55 % for CA19-9). The serum LDH levels were significantly higher in older patients (p = 0.05) and also in the patients with large tumors (p = 0.05), hepatic metastasis (p = 0.01), hypoalbuminemia (p = 0.01), and unresponsive to chemotherapy (p = 0.04). However, no correlation was found between both serum CEA and CA19-9 levels and possible prognostic factors (p > 0.05). The significant relationships were found between the serum levels of CEA and CA19-9 (r s = 0.24, p = 0.004), and serum LDH and CEA (r s = 0.193, p = 0.02). But, there was no correlation between serum LDH and CA19-9 levels (p = 0.39). One-year overall survival rate was 12.8 % (95 % CI 8–18). Increased serum levels of all the tumor markers significantly had adverse affect on survival (p = 0.001 for LDH, p = 0.002 for CEA, and p = 0.007 for CA19-9). However, no difference was observed in between high levels and very high levels of serum markers for all tumor markers (p > 0.05). Patients with normal serum levels of all three tumor markers had better outcome than others (p = 0.002) and those with normal serum LDH and CEA levels (whatever CA19-9) levels had associated with better survival compared with other possible alternatives (p < 0.001).Conclusion
Serum levels of LDH, CEA, and CA19-9 had significant affect on survival in MPC patients. 相似文献12.
C.-C. Lin C.-Y. Liu M.-J. Chen T.-E. Wang C.-H. Chu H.-Y. Wang S.-C. Shih M.-L. Hsu T.-C. Hsu Y.-J. Chen 《Clinical & translational oncology》2013,15(10):855-860
Introduction
This research aimed to demonstrate the correlation of circulating endothelial cells (CECs) count and serum cytokine levels with side effects and prognosis in rectal cancer patients receiving adjuvant chemoradiation.Methods
Eleven patients received proctectomy, chemoradiotherapy and follow-up for 4 years. Fifty-five blood samples were taken before radiation and during the course. The quantities of CECs were estimated by flow cytometry, and serological factors were measured by ELISA.Results
The CEC level in patients without tumor recurrence was significantly lower than in patients with tumor recurrence (p < 0.01). The IL-6 and TGF-β1 levels exhibited a similar profile (p < 0.01). For morbidity, the mean CEC level in patients with grade 3 diarrhea was significantly greater than patients with grades 1 (p < 0.001) and 2 diarrhea (p < 0.005).Conclusions
Levels of CECs, serum IL-6, TGF-β1 and TNF-α during post-operative chemoradiation in rectal cancer patients might be candidate biomarkers for prognosis and morbidity (NCT00325871). 相似文献13.
Y. Homma K. Taniguchi M. Nakazawa R. Matsuyama R. Mori K. Takeda Y. Ichikawa K. Tanaka I. Endo 《Clinical & translational oncology》2014,16(3):330-335
Purpose
Regulatory T cells (Tregs) play a role in the immunosuppressive state in pancreatic cancer patients. We aimed to evaluate the changes of immune cells population including Tregs caused by gemcitabine (GEM)-based chemotherapy.Methods
Fifty-three patients with pancreatic cancer were enrolled in this study, of which 32 received GEM- based chemotherapy. Blood samples were collected before and at least 2 weeks after the last dose of chemotherapy. The peripheral blood mononuclear cells (PBMCs) were subjected to flow cytometry analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Other lymphocytes and NK cell markers were also measured. The proliferative capacity of PBMCs stimulated with anti-CD3 was analyzed using H3 thymidine.Results
The percentage and number of Tregs were significantly decreased after chemotherapy (p = 0.032, p = 0.003, respectively). The other immune cells and the proliferative capacity did not change.Conclusion
This study showed that GEM-based chemotherapy produced an immunomodulatory effect via the depletion of Tregs. 相似文献14.
F. Pietrantonio P. Biondani M. Milione F. Melotti G. Bertarelli F. Perrone F. de Braud L. Mariani G. Fanetti D. Cortinovis M. Di Bartolomeo 《Clinical & translational oncology》2013,15(7):582-586
Background
Currently, first-line chemotherapy in advanced colorectal cancer is not tailored on predictive biomarkers. Bax proapoptotic protein may correlate to chemosensitivity and differential response to irinotecan or oxaliplatin-based combinations.Methods
Bax expression was assessed by immunohistochemistry in 49 advanced colorectal cancer patients enrolled at our institution from 2002 to 2004 within a multicenter, phase II, randomized trial of first-line UFT/leucovorin/irinotecan (TEGAFIRI) versus UFT/leucovorin/oxaliplatin (TEGAFOX).Results
Bax-positive and negative samples were 49 and 51 %. Response was significantly lower in Bax positive (25 %) as compared to Bax negative (56 %) (Odds ratio = 0.26; p = 0.03). No significant difference was noted in TEGAFOX subgroup; in TEGAFIRI arm, responses were lower in Bax positive (18 %) than Bax negative (67 %) (Odds ratio = 0.11; p = 0.03). No difference in terms of progression-free and overall survival was observed according to Bax.Conclusion
Bax-negative colorectal cancer may identify a specific phenotype of patients with significantly higher chance to respond to doublet irinotecan-based chemotherapy. 相似文献15.
Akiko Kawano Takako Eguchi Nakajima Ichiro Oda Nobukazu Hokamura Satoru Iwasa Ken Kato Tetsuya Hamaguchi Yasuhide Yamada Hirofumi Fujii Yasuhiro Shimada 《Gastric cancer》2014,17(1):54-60
Background
There have been no reports on the incidence, characteristics, treatment outcomes, and prognosis of inoperably advanced or recurrent adenocarcinoma of the esophagogastric junction (AEGJ) in Japan.Methods
We investigated the clinicopathological characteristics, treatment outcomes, and prognosis for 816 patients with esophagogastric junctional and gastric adenocarcinoma who received first-line chemotherapy between 2004 and 2009.Results
Of 816 patients, 82 (10 %) had AEGJ. The patients with AEGJ had significantly more lung and lymph node metastasis, but less peritoneal metastasis, than those with gastric adenocarcinoma (GAC). The objective response rate to first-line chemotherapy was 23.3 % for patients with AEGJ and 22.6 % in patients with GAC (p = 0.90). The median survival was 13.0 months in AEGJ and 11.8 months in GAC (p = 0.445). In no patient was tumor site a significant prognostic factor (p = 0.472). In patients with AEGJ, ECOG PS ≥ 2, presence of liver metastasis, and absence of lung metastasis were significantly associated with poor prognosis.Conclusions
No significant differences were observed in treatment outcomes between advanced AEGJ and GAC. Therefore, the same chemotherapy regimen can be given as a treatment arm in future Japanese clinical trials to both patients with inoperably advanced or recurrent AEGJ and those with GAC. 相似文献16.
Sachi Morita Keisuke Uehara Goro Nakayama Takashi Shibata Tomoyo Oguri Megumi Inada-Inoue Tomoya Shimokata Mihoko Sugishita Ayako Mitsuma Yuichi Ando 《Cancer chemotherapy and pharmacology》2013,71(2):405-411
Purpose
Bevacizumab, a monoclonal antibody that binds to VEGF, has a well-known toxic effect of hypertension. We studied possible associations between bevacizumab-related hypertension and gene polymorphisms to assure safer cancer therapy.Methods
We retrospectively studied 60 Japanese patients with metastatic colorectal cancer who had received bevacizumab-based chemotherapy. Genotypes were determined for five well-known functional single-nucleotide polymorphism of the VEGF gene at positions C-2578A, T-1498C, G-1154A, G-634C, and C936T. Hypertension was graded according to CTCAE v4.0 on the basis of home blood pressure.Results
The VEGF-2578 C/C and -1498 T/T genotypes were associated with significantly less hypertension during the first 2 months of bevacizumab-based chemotherapy (p = 0.004, p = 0.025, respectively). During the treatment period as a whole, the VEGF-2578 C/C and 936 C/C genotypes were associated with less hypertension (p = 0.031, p = 0.043, respectively). Preexisting hypertension was not associated with bevacizumab-related hypertension.Conclusions
This study demonstrated a significant relation between a lower incidence of grade 2 or higher bevacizumab-related hypertension and the VEGF-2578 C/C genotype for the entire treatment period in Japanese patients with metastatic colorectal cancer. This genotype might be useful for ensuring safer treatment of patients who receive bevacizumab-based chemotherapy. 相似文献17.
Huyen Pham Benjamin M. Schwartz James E. Delmore Eddie Reed Scott Cruickshank Leanne Drummond Kathleen E. Rodgers Kainoa J. Peterson Gere S. diZerega 《Cancer chemotherapy and pharmacology》2013,71(4):965-972
Purpose
This randomized, double-blind, placebo-controlled Phase 2 study evaluated safety and efficacy of A(1–7) for reduction in Grade 3–4 thrombocytopenia in patients receiving myelosuppressive chemotherapy. Pharmacodynamic activity of A(1–7) in platelet production and retention of scheduled dose intensity were also determined.Methods
Thirty-four patients with ovarian, Fallopian tube, or peritoneal carcinoma receiving gemcitabine and carboplatin or cisplatin were evaluated. Patients were randomized to receive study drug subcutaneously at 100 mcg/kg (n = 11), 300 mcg/kg (n = 13), or placebo (n = 10) following chemotherapy for up to six cycles. Hematologic variables were obtained throughout each treatment cycle.Results
There were no drug-related safety issues. There were no instances of Grade 4 thrombocytopenia in patients who received 100 mcg/kg treatment compared to 6 % of chemotherapy cycles for patients receiving placebo (p = 0.07). The maximal percentage increase in platelet concentration from baseline was higher for patients who received 100 mcg/kg A(1–7) compared to placebo (p = 0.02). This increase was accompanied by a reduction in the nadir absolute neutrophil count (p = 0.04). Relative dose intensity for the combination chemotherapy was higher for patients who received 100 mcg/kg A(1–7) compared to placebo (p = 0.04). There were no differences in outcomes for patients receiving 300 mcg/kg dose compared to placebo.Conclusions
A 100 mcg/kg dose of A(1–7) was shown to produce pharmacodynamic effects on peripheral blood platelet counts, preserve planned dose intensity, and reduce Grade 3–4 thrombocytopenia following gemcitabine and platinum chemotherapy. These findings are consistent with A(1–7)-induced stimulation of thrombogenesis in the bone marrow following marrow-toxic chemotherapy. 相似文献18.
Ji-Won Kim Jee Hyun Kim Seock-Ah Im Yu Jung Kim Hye-Suk Han Jin-Soo Kim Kyung-Hun Lee Tae-Yong Kim Sae-Won Han Yoon Kyung Jeon Do-Youn Oh Tae-You Kim In Ae Park 《Cancer chemotherapy and pharmacology》2013,72(1):109-115
Purpose
This study aimed to elucidate the clinical implication of human epidermal growth factor receptor 2/centromeric probe for chromosome 17 (HER2/CEP17) ratio and HER2 immunohistochemistry (IHC) results in patients with HER2 fluorescence in situ hybridization (FISH)-positive metastatic breast cancer (MBC) who received first-line trastuzumab plus taxane chemotherapy.Methods
Using clinical data of patients with HER2 FISH-positive MBC who received first-line trastuzumab plus taxane chemotherapy, we analyzed the clinical outcome according to the HER2/CEP17 ratio and HER2 IHC analysis.Results
Fifty-two women were analyzed. The median age was 50 years (range 27–69 years). Patients with a HER2/CEP17 ratio ≥3.0 had significantly longer progression-free survival (PFS) (17.2 vs. 7.4 months; p = 0.002) with a tendency toward higher response rate (RR) (p = 0.325) and longer overall survival (OS) (p = 0.129). Patients with HER2 IHC 1+ had significantly shorter OS (14.0 vs. 42.4 months; p = 0.013) along with a tendency toward lower RR (p = 0.068) and shorter PFS (p = 0.220). In the multivariate analysis, HER2/CEP17 ratio <3.0 (p = 0.004) and Eastern Cooperative Oncology Group (ECOG) PS 2 (p = 0.015) were significant factors for shorter PFS, and HER2 IHC 1+ (p = 0.015) and ECOG PS 2 (p = 0.036) were significant factors for poor OS.Conclusions
Our data support that HER2/CEP17 ratios and HER2 IHC scores may predict clinical outcome after first-line trastuzumab plus taxane chemotherapy in patients with HER2 FISH-positive MBC. 相似文献19.
O. Juan J. Vidal R. Gisbert J. Muñoz S. Maciá J. Gómez-Codina 《Clinical & translational oncology》2014,16(7):637-643
Purpose
To evaluate the association in the change of circulating tumor cell (CTC) levels and clinical outcomes (PFS and OS) in patients with advanced non-small cell lung cancer (NSCLC) treated homogenously with docetaxel and gemcitabine administered every 2 weeks.Methods
We prospectively evaluated 37 patients for CTC levels at baseline and after 2 months of chemotherapy (before third cycle). Detection was carried out with the CellSearch system.Results
Nine of the 37 patients (24 %) had ≥2 CTCs at the baseline determination. Median progression-free survival (PFS) was 4.3 months (95 % CI 2.5–8.3) for patients with CTC 0–1 as compared to 9.4 months (95 % CI 1.2–12.2) for those with CTC ≥2 (p = 0.3506). Median overall survival (OS) was 8.1 (95 % CI 2.8–16.3) and 12.2 (95 % CI 1.4–12.2) months for patients with 0–1 CTCs and ≥2 CTCs, respectively (p = 0.7639). Patients with a second CTC quantification were classified as: group 1, CTC = 0–1 at baseline and CTC = 0–1 after second chemotherapy cycle (18 patients); group 2, CTC ≥2 at baseline and CTC = 0–1 after second determination (5 patients). Median PFS was 7.7 and 9.9 months for group 1 and group 2, respectively (p = 0.4467).Conclusions
CTCs ≥2 at baseline were detected only in 24 % of this group of patients with advanced NSCLC and poor performance status. No significant differences in PFS and OS between patients with or without CTCs at baseline were observed. 相似文献20.
Yuka Kato Katsuyuki Hotta Nagio Takigawa Naoyuki Nogami Toshiyuki Kozuki Akiko Sato Eiki Ichihara Kenichiro Kudo Isao Oze Masahiro Tabata Tetsu Shinkai Mitsune Tanimoto Katsuyuki Kiura 《Cancer chemotherapy and pharmacology》2014,73(5):943-950