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Preview: Japanese Journal of Clinical Oncology - current issue

Japanese Journal of Clinical Oncology Current Issue





Published: Thu, 10 Aug 2017 00:00:00 GMT

Last Build Date: Tue, 29 Aug 2017 05:44:53 GMT

 






IN THIS ISSUE

2017-08-04




Joint Symposium of Korean Cancer Association & UICC-ARO—Cross-boundary cancer studies: cancer and Universal Health Coverage (UHC) in Asia

2017-07-19

Abstract
On 16 June 2016, the Korean Cancer Association (KCA) and Union for International Cancer Control-Asia Regional Office (UICC-ARO) organized a joint symposium as part of the official program of the 42nd Annual Meeting of the Korean Cancer Association to discuss the topic ‘Cross-boundary Cancer Studies: Cancer and Universal Health Coverage (UHC) in Asia.’ Universal Health Coverage is included in the Sustainable Development Goals adopted by the United Nations as part of the 2030 Agenda for Sustainable Development. The objectives of UHC are to ensure that all people can receive high-quality medical services, are protected from public health risks, and are prevented from falling into poverty due to medical costs or loss of income arising from illness. The participants discussed the growing cost of cancer in the Asian region and the challenges that this poses to the establishment and deployment of UHC in the countries of Asia, all of which face budgetary and other systemic constraints in controlling cancer in the region. Representatives from Korea, Japan and Indonesia reported on the status of UHC in their countries and the challenges that are being faced, many of which are common to other countries in Asia. In addition to country-specific presentations about the progress of and challenges facing UHC, there were also presentations from WHO Kobe Centre concerning advancing UHC in non-communicable diseases and prospects for further collaboration and research on UHC. A presentation from the University of Tokyo also highlighted the need to focus on multidisciplinary studies in an age of globalization and digitization.






Antitumor activity of iNGR-GRIM-19 in colorectal cancer

2017-07-05

Abstract
Background
Gene associated with retinoid-interferon induced mortality-19 (GRIM-19) plays crucial roles in carcinogenesis.
Objective
To explore the antitumor activity of internalizing NGR (iNGR) gene associated with GRIM-19 in colorectal cancer.
Methods
Cells were incubated with fluorescein isothiocyanate-labeled fusion proteins followed by fluorescence microscopic analysis. Cell proliferation was determined by MTT assay. Cell cycle was analyzed by flow cytometric analysis. Cell migration and invasion capacity were evaluated by wound scratch and Transwell assays, respectively. Apoptosis was measured by Annexin V/PI staining and TUNEL assay. Gene expressions were determined by RT-PCR and Western blotting. Nude mice bearing colorectal cancer received vehicle, GRIM-19, or iNGR-GRIM-19 fusion protein injection, and the in vivo antitumor capacity of the fusion proteins was examined.
Results
iNGR-GRIM-19 was specifically taken up by human colorectal cancer Colo205 cells, but not corneal epithelial (HCEpic) cells, whereas GRIM-19 was not internalized by either cell type. Unlike GRIM-19, incubation with iNGR-GRIM-19 dose-dependently inhibited proliferation, induced G1 phase arrest, suppressed cell migration and invasion, and caused apoptosis in Colo205 cells. Additionally, injection of iNGR-GRIM-19 extended the lifespan of colorectal cancer-bearing nude mice and reduced in vivo tumor growth as compared with vehicle or GRIM-19 treatment. iNGR-GRIM-19 was localized only in the tumor mass, without affecting other tissues, such as liver or kidney. iNGR-GRIM-19 injection led to G1 phase arrest and induced cell apoptosis in xenografted colorectal cancer tissues.
Conclusions
iNGR-GRIM-19 has an efficient antitumor activity in vitro and in vivo, and might be a promising agent for the treatment of colorectal cancer.



Local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer

2017-07-05

Abstract
Background
Radiotherapy is an effective treatment for the postoperative loco-regional recurrence of esophageal cancer; however, the optimal treatment field remains controversial. This study aims to evaluate the outcome of local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.
Methods
We retrospectively investigated 35 patients treated for a postoperative loco-regional recurrence of esophageal cancer with local field radiotherapy between December 2008 and March 2016. The median irradiation dose was 60 Gy (range: 50–67.5 Gy). Thirty-one (88.6%) patients received concurrent chemotherapy.
Results
The median follow-up period was 18 months (range: 5–94 months). The 2-year overall survival was 55.7%, with a median survival time of 29.9 months. In the univariate analysis, the maximal diameter ≤20 mm (P = 0.0383), solitary lesion (P = 0.0352), and the complete remission after treatment (P = 0.00411) had a significantly better prognosis. A total of 27 of 35 patients (77.1%) had progressive disease (loco-regional failure [n = 9], distant metastasis [n = 7], and both loco-regional failure and distant metastasis [n = 11]). No patients had Grade 3 or greater mucositis.
Conclusion
Local field radiotherapy is a considerable treatment option for postoperative loco-regional recurrence of esophageal cancer.



Retrospective analysis of definitive radiotherapy for neck node metastasis from unknown primary tumor: Japanese Radiation Oncology Study Group study

2017-07-05

Abstract
Objective
To investigate the optimal treatment method and risk factor of neck node metastasis from unknown primary tumors (NUP) treated by radiotherapy.
Methods
Retrospective case study based on a multi-institutional survey was conducted by the Japanese Radiation Oncology Study Group. Patients pathologically diagnosed as having NUP from 1998 to 2007 were identified. Univariate and multivariate analyses of overall survival (OS), progression free survival (PFS), neck progression free survival (NPFS) and mucosal progression free survival (MPFS) were evaluated.
Results
In total, 130 patients with median age of 65 years were included. Nodal stages N1, N2a, N2b and N2c were observed for 10, 26, 43, 12 and 39 patients, respectively. All the patients received radiotherapy (RT) with neck dissection in 60 and with chemotherapy in 67 cases. The median doses to the metastatic nodes, prophylactic neck and prophylactic mucosal sites were 60.0, 50.4 and 50.4 Gy, respectively. The median follow-up period for surviving patients was 42 months. Among 12 patients, occult primary tumors in the neck region developed after radiotherapy. The 5-year OS, PFS, NPFS and MPFS were 58.1%, 42.4%, 47.3% and 54.9%, respectively. Univariate analysis showed that lower N stage (N1–2b), non-bulky node (<6 cm) and negative extracapsular extension (ECE) status were the factors associated with favorable OS, PFS, NPFS and MPFS. Radical surgery proved to be a favorable factor of OS, NPFS and MPFS. On multivariate analysis, lower N stage and negative ECE status were correlated with improved survival.
Conclusions
Lower nodal stage and negative ECE status showed a favorable impact on survival and disease control in patients with NUP treated by radiotherapy.



Sex differences in lung cancer survival: long-term trends using population-based cancer registry data in Osaka, Japan

2017-07-05

Abstract
Objective
Several studies of sex differences in lung cancer survival have been reported. However, large-size population-based studies based on long-term observation are scarce. We investigated long-term trends in sex differences in lung cancer survival using population-based cancer registry data from Osaka, Japan.
Methods
We analyzed 79 330 cases from the Osaka Cancer Registry (OCR) diagnosed between 1975 and 2007. We calculated 5-year relative survival in the six periods (1975–1980, 1981–1986, 1987–1992, 1993–1997, 1998–2002 and 2003–2007). To estimate the trends in sex differences in lung cancer survival throughout the study period, we applied a multivariate excess hazard model to control for confounders.
Results
The proportion of adenocarcinoma (ADC) and 5-year relative relative survival have increased for both sexes. Sex differences in lung cancer survival have widened over the period, especially in ADC and since the late 1990s. The excess hazard ratio of death within 5 years for males was 1.19 (95% CI: 1.16–1.21), adjusting for period at diagnosis, histologic type, stage, age group and treatment.
Conclusion
We reported that females have better prognosis in lung cancer than males and the sex differences in lung cancer survival have become wider in Osaka, Japan. This can be partly explained by the sex differences in the proportions of histologic type and stage. Further studies considering other factors that influence sex differences in lung cancer survival are needed.



Adherence to oral chemotherapy medications among gastroenterological cancer patients visiting an outpatient clinic

2017-06-17

Abstract
Objective
The purpose of this study was to investigate medication adherence to oral chemotherapy medications and determinants of medication non-adherence to them among gastroenterological cancer patients.
Methods
A cross-sectional study was conducted on 117 consecutive, consenting, eligible patients visiting an outpatient clinic of university hospital in Japan. Good medication adherence was defined as taking 100% of the prescribed dose. Medication adherence was measured via self-report. We hypothesized that there was a significant relationship between medication non-adherence and the five factors defined by the World Health Organization: patient-related, socioeconomic-related, condition-related, treatment-related, and healthcare-system/provider-related factors. Multiple logistic regression models were used to identify factors associated with oral chemotherapy medication non-adherence.
Results
The proportion of patients showing good medication adherence was 56.4%. The multiple logistic regression analysis revealed that the determinants of medication non-adherence to oral chemotherapy medications included having a history of patient-caused treatment interruptions due to worsening of symptoms (adjusted odds ratio [AOR] = 9.59, 95% confidence interval [CI] = 1.38–66.47), having diarrhea (AOR = 3.25, 95% CI = 1.13–9.34), experiencing pain (AOR = 0.17, 95% CI = 0.05–0.55), taking oral chemotherapy medication every 8 h (AOR = 5.52, 95% CI = 1.71–17.81), and diminished sense of priority for medication (AOR = 1.40, 95% CI = 1.21–1.63).
Conclusions
This study suggests that many patients with gastroenterological cancer were non-adherent to oral chemotherapy medications. It might be necessary to conduct periodic screening and connect patients at a high risk of medication non-adherence to appropriate support.



A Phase II study of palonosetron, aprepitant, dexamethasone and olanzapine for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in patients with thoracic malignancy

2017-06-17

Abstract
Background
The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients.
Methods
We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1–5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0–120 h post-chemotherapy).
Results
Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36–75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0–24 h post-chemotherapy), delayed (24–120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70–92%; 95% confidence interval: 66–93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine.
Conclusions
The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy.



Efficacy of early ureteral ligation on prevention of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma: a prospective single-arm multicenter clinical trial

2017-06-14

Abstract
Objective
The rate of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma is high. Seeding upper urinary tract urothelial carcinoma cells onto the damaged bladder wall is considered to be one of the causes of intravesical recurrence after radical nephroureterectomy. We evaluated the utility of early ureteral ligation in preventing the intravesical recurrence.
Methods
This prospective single-arm clinical trial included patients who underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma in the Tohoku Urological Evidence-Based Medicine Study Group between 2012 and 2013. Early ureteral ligation was defined as ligation of the ureter as quickly as possible after expanding the retroperitoneal space. A historical control was extracted from 454 patients who underwent radical nephroureterectomy in the same group, using propensity score-matched analysis. Intravesical recurrence-free survival rates were analyzed using Kaplan–Meier curves. Factors predicting intravesical recurrence were assessed using multivariate analyses.
Results
Seventy-four patients underwent early ureteral ligation. Seventeen (23%) patients had intravesical recurrence with a median follow-up period of 24 months. The 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 81% and 76%, and in the control group 75% and 63%, respectively (P = 0.160). In patients with renal pelvic cancer, the 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 89% and 86%, but in the control group 74% and 64%, respectively (P = 0.025). However, intravesical recurrence-free survival rates were similar in patients with ureteral cancer. Multivariate analyses of a subset of patients with renal pelvic cancer identified early ureteral ligation as an independent predictor of intravesical recurrence.
Conclusions
Early ureteral ligation decreases the rate of intravesical recurrence after radical nephroureterectomy in patients with renal pelvic cancer. Thus, early ureteral ligation might help in prevention of intravesical recurrence for renal pelvic cancer.



The effect of predisposing atheroembolic risk factors on renal functional recovery between laparoscopy and open technique in patients with T1-stage renal cell carcinoma who underwent partial nephrectomy: a retrospective comparison study

2017-06-14

Abstract
Objective
The present study aimed to determine the effect of an increasing number of predisposing atheroembolic risk factors on the development of chronic kidney disease (CKD) after partial nephrectomy (PN) in patients with T1-stage renal cell carcinoma (RCC).
Methods
The study included 147 patients with T1-stage RCC with a normal contralateral kidney and without preoperative CKD, who underwent open (OPN, N = 83, 56.5%) or laparoscopic PN (LPN, N = 64, 43.5%) between 2003 and 2014. Postoperative CKD was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2. The predictive factors for CKD between OPN and LPN were statistically assessed among various known clinicopathological factors associated with renal function in PN with a significance of two-sided P value <0.05.
Results
During a median follow-up of 42 months, the recurrence rate was 0.7% (n = 1), and the rate of postoperative CKD was 11.6% (n = 17). Significant differences in CKD-free survival were observed among patients with atheroembolic risks 5–7, 3–4 and 1–2 (P = 0.027). Regarding the predictive factors for the postoperative development of CKD between OPN and LPN, a predisposing atheroembolic risk ≥3 was significant among other clinicopathological factors in multivariate analysis (hazard ratio, 3.007, P = 0.031).
Conclusion
Patients with T1-staged RCC with ≥3 predisposing atheroembolic risk factors have a significantly higher risk of developing CKD after PN. Patients who underwent LPN had a lesser incidence of CKD development than patients who underwent OPN with ≥3 predisposing atheroembolic risk factors.



Severe esophagitis associated with cytomegalovirus during concurrent chemoradiotherapy for esophageal cancer

2017-06-07

Abstract
Although radiation esophagitis is one of the most common adverse events that occurs during chemoradiotherapy (CRT) in patients with esophageal cancer, CRT-associated cytomegalovirus (CMV) esophagitis is rare. CMV esophagitis typically occurs in patients with an immunosuppressed status. Here we report a case of CMV esophagitis during CRT initially treated as radiation esophagitis. A 64-year-old man with mid-thoracic esophageal cancer was admitted to our hospital with clinical stage cT4bN1M1 (supraclavicular lymph node metastasis) Stage IV according to the UICC ver. 7 guidelines, and he was administered definitive concurrent CRT. From the 39th day of CRT onwards, he presented with a sustained fever and severe odynophagia that was resistant to antibiotic therapy. An esophagoscopy revealed severe esophagitis with a circumferential ulcer throughout the entire esophagus, and CMV esophagitis was clinically suspected because of positive result of CMV antigenemia. Subsequently, antiviral therapy for CMV provided dramatic relief of his symptoms. Later, CMV DNA was confirmed with a polymerase chain reaction in the biopsy specimen.The symptoms of CMV esophagitis resemble those of radiation esophagitis and can make the diagnosis difficult. Thus, CMV esophagitis associated CRT may be overlooked or masked by radiation esophagitis and can cause a delay in healing. Therefore, CMV esophagitis may be considered when severe intractable esophagitis is observed during CRT.



Is preoperative spirometry a predictive marker for postoperative complications after colorectal cancer surgery?

2017-06-07

Abstract
Background
Spirometry is a basic test that provides much information about pulmonary function; it is performed preoperatively in almost all patients undergoing colorectal cancer (CRC) surgery in our hospital. However, the value of spirometry as a preoperative test for CRC surgery remains unknown. The aim of this study was to determine whether spirometry is useful to predict postoperative complications (PCs) after CRC surgery.
Methods
The medical records of 1236 patients who had preoperative spirometry tests and underwent CRC surgery between 2005 and 2014 were reviewed. Preoperative spirometry results, such as forced vital capacity (FVC), one-second forced expiratory volume (FEV1), %VC (FVC/predicted VC) and FEV1/FVC (%FEV1), were analyzed with regard to PCs, including pneumonia.
Results
PCs were found in 383 (30.9%) patients, including 218 (56%) with surgical site infections, 67 (17%) with bowel obstruction, 62 (16%) with leakage and 20 (5.2%) with pneumonia. Of the spirometry results, %VC was correlated with PC according to logistic regression analysis (odds ratio, OR = 0.99, 95% confidence interval, CI = 0.98–0.99; P = 0.034). Multivariate analysis after adjusting for male sex, age, laparoscopic surgery, tumor location, operation time and blood loss showed that a lower %VC tends to be a risk factor for PC (OR = 0.99, 95% CI = 0.98–1.002; P = 0.159) and %VC was an independent risk factor for postoperative pneumonia in PCs (OR = 0.97, 95% CI = 0.94–0.99; P = 0.049).
Conclusions
In CRC surgery, %VC may be a predictor of postoperative complications, especially pneumonia.



Efficacy of radiotherapy for primary tumor in patients with unresectable pancreatic neuroendocrine tumors

2017-06-07

Abstract
Background
Detailed information regarding the clinical efficacy of radiotherapy (RT) for primary tumor in patients with unresectable pancreatic neuroendocrine tumors (pNETs) is unknown. We therefore performed a retrospective study to evaluate the efficacy and safety of RT for primary pancreatic tumors in patients with pNETs.
Methods
We investigated 11 patients with pNETs who received RT to the primary site between January 1997 and June 2015. Seven patients had Grade 2 neuroendocrine tumors (NET-G2) and four had neuroendocrine carcinoma (NEC) according to the 2010 WHO histopathological classification.
Results
The tumor response and control rates were 27.2% and 100%, respectively (3: partial response, 8: stable disease). Among patients with NET-G2 tumors, the response rate was 28.5% (2/7 patients) and symptomatic improvement was noted in 33.3% of the patients (1/3 patients). The response rate for patients with NEC were 25% (1/4), one NEC patients with symptoms exhibited symptomatic improvement. The median overall survival and median progression-free survival were 35.9 months and 5.5 months, respectively. Grade 3 diarrhea as an acute toxicity and Grade 3 gastrointestinal hemorrhage as a late toxicity were observed.
Conclusions
RT to the primary cancer site in patients with pNETs was an effective modality for local disease control and the treated patients had good outcomes. If metastatic tumors are under control, RT to the primary site may be beneficial for patients with pNETs.



Yokukansan for the treatment of preoperative anxiety and postoperative delirium in colorectal cancer patients: a retrospective study

2017-06-07

Abstract
Background
Yokukansan (YKS), a Japanese traditional herbal medicine for neurosis and insomnia, is speculated to be useful for perioperative psychiatric symptoms in cancer patients, but there exists little empirical evidence. This study provides preliminary data about the efficacy, feasibility, and side effects of YKS for the treatment of preoperative anxiety and postoperative delirium in cancer patients.
Methods
We retrospectively reviewed the medical records of colorectal cancer patients who took YKS for preoperative anxiety, evaluating the following: (1) patient characteristics, (2) feasibility of taking YKS, (3) changes in preoperative anxiety based on the Clinical Global Impression (CGI) scale and Edmonton Symptom Assessment System-revised (ESAS-r-anxiety), (4) incidence of postoperative delirium and (5) YKS-related side effects.
Results
We reviewed 19 medical records. There was a significant difference between ESAS-r-anxiety scores (P = 0.028) before and after taking YKS, but no difference between CGI scores (P = 0.056). The incidence of postoperative delirium was 5.2% (95% CI = 0.0–14.5). One patient could not complete the course of YKS during the perioperative administration period, but there were no side effects of Grade 2 or worse according to the Common Terminology Criteria for Adverse Events v4.
Conclusions
Cancer patients could safely take YKS before surgery. There was a significant improvement in preoperative anxiety after taking YKS, and the incident rate of postoperative delirium was lower than in previous studies. These results suggest that YKS may be useful for perioperative psychiatric symptoms in cancer patients. Further well-designed studies are needed to substantiate our results.



Optimism, pessimism and self-efficacy in female cancer patients

2017-06-07

Abstract
Objective
The aim of this examination was to study whether psychological resource variables (optimism and self-efficacy) decrease when cancer is present and to test the predictive power of these variables for anxiety, depression and quality of life (QoL).
Methods
The patient sample was comprised of 354 German women suffering from breast cancer or gynecological cancer. Participants filled in the resource assessment tools Life Orientation Test-Revised and the General Self-Efficacy Scale as well as the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire-4 and the QoL instrument EORTC QLQ-C30 at two time points: (t1) during patients’ hospital stay and (t2) 3 months later.
Results
The mean scores for optimism (total score: M = 16.2) and self-efficacy (M = 29.8) were even somewhat higher than the corresponding means of the general population. Optimism and self-efficacy were positively correlated with QoL (r between 0.15 and 0.17, P < 0.01) and negatively associated with anxiety and depression (r between −0.17 and −0.36, P < 0.01). However, only optimism was predictive of the t2 anxiety, depression and QoL scores when statistically taking into account the baseline levels of the outcome variables.
Conclusions
Having cancer does not generally reduce optimism and self-efficacy on the level of patients’ mean scores. Cancer patients with a high level of habitual optimism will adapt to their disease better than pessimistic patients, even if the baseline levels of the outcome variables have been accounted for.



Effective chemomobilization with etoposide and cytarabine (EC regimen) in lymphoma patients: a single-center, retrospective, observational study

2017-05-24

Abstract
Objective
Autologous stem cell transplantation is an important strategy for patients with relapsed or refractory lymphoma. Although various regimens for peripheral blood stem cell collection have been used, the optimal regimen has not yet been established. We aimed to evaluate the mobilization efficacy and safety of the regimen consisted of etoposide and cytarabine (EC regimen).
Methods
We retrospectively analyzed the clinical data of 46 lymphoma patients who received peripheral blood stem cell mobilization with the EC regimen [etoposide (100 mg/m2/day, days 1–4) and cytarabine (100 mg/m2/day, days 1–4)] at Toyohashi municipal hospital from 2004 to 2013.
Results
The median age of the patients was 55 years. The most common underlying diseases were diffuse large B-cell lymphoma (46%) and follicular lymphoma (26%). Three-quarters of patients were in their second complete or partial remission. The median total number of collected CD34+ cells was 10.6 × 106 kg–1. Forty-two patients (91%) yielded at least 2 × 106 kg–1 CD34+ cells within a median of 2 apheresis days, and 33 patients (72%) achieved it with only one apheresis. Successful mobilization was observed in five of six patients who failed to mobilize previously. Although febrile neutropenia occurred in 22 patients (48%), no fatal infection was observed.
Conclusion
The EC regimen was highly effective in lymphoma patients, including patients who mobilized poorly with other regimens.



Postmarketing surveillance study of erlotinib plus gemcitabine for pancreatic cancer in Japan: POLARIS final analysis

2017-05-24

Abstract
Objective
Erlotinib plus gemcitabine is approved in Japan for the treatment of metastatic pancreatic cancer. The POLARIS surveillance study investigated safety (focusing on interstitial lung disease [ILD]) and efficacy of erlotinib plus gemcitabine in Japanese pancreatic cancer patients.
Methods
Patients receiving erlotinib plus gemcitabine for pancreatic cancer in Japan between July 2011 and August 2012 were enrolled. ILD-like events were independently confirmed by a review committee. Overall survival (OS) and progression-free survival (PFS) were assessed, and risk factors for ILD occurrence were analyzed by multivariate Cox regression analysis.
Results
Safety data were available for 843 patients and efficacy data for 841. Adverse drug reactions were reported in 83.5% of patients, no new safety signals were identified. ILD events were confirmed by the review committee in 52 patients (6.2%), with two fatal cases (0.2%). Median time from initial erlotinib treatment to ILD events was 70.5 days. Of the 52 patients with ILD events, 86.5% improved or fully recovered from ILD (median time 24 days). Multivariate analysis identified previous or concurrent lung disease (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.0–4.5; P = 0.0365) and ≥3 organs with metastases (HR, 4.2; 95% CI, 2.2–8.2; P < 0.0001) as potential ILD risk factors. Accumulated OS rate at 28 weeks was 68.2%, and median PFS was 92 days (95% CI, 86–101).
Conclusions
Erlotinib plus gemcitabine has an acceptable safety and efficacy profile in pancreatic cancer; however, patients should be assessed for previous/concurrent lung disease and metastatic burden, before and during treatment.



Cardiovascular toxic effects of targeted cancer therapy

2017-05-20

Abstract
Over the past decade, there has been a major shift in chemotherapy from non-specific cytotoxic drugs to molecular targeted drug therapies. As more molecular targeted therapies are developed, new types of cardiovascular toxicities induced by targeted therapies are a growing problem. Cardiotoxicity induced by the human epidermal growth factor receptor-2 inhibitor trastuzumab manifests as decreased left ventricular ejection fraction. In contrast to anthracycline treatment, most cardiac events occur during trastuzumab treatment, but are reversed quickly when treatment is interrupted and cardiac intervention is established. Vascular endothelial growth factor pathway inhibitors decrease vascular tone, leading to hypertension. After drug initiation, the early detection and aggressive pharmacological management of hypertension are necessary to avoid severe complications. Cardiovascular safety is an emerging challenge in patients treated with newer generations of BCR-ABL inhibitors. Although rare, dasatinib-induced pulmonary hypertension is potentially fatal. Vascular events including cardiac and cerebral ischemic events and peripheral arterial occlusive disease have emerged as a new type of toxicity in patients treated with ponatinib and nilotinib. Thus, a wide variety of cardiovascular toxicities have been observed in patients treated with targeted drugs and have become a critically important topic of discussion for the practicing oncologist and cardiologists. Awareness of the potential side effects, recognition of signs and symptoms, and the establishment of therapeutic strategies are all crucial to providing quality patient care.