Impact of delirium on the short term prognosis of advanced cancer patients. Italian Multicenter Study Group on Palliative Care

BACKGROUND: The objective of this study was to evaluate the impact of delirium on the survival of advanced cancer patients also assessed with a validated prognostic score (the palliative prognostic [PaP] score). METHODS: The study population was a prospective multicenter consecutive case series of advanced cancer patients for whom chemotherapy was no longer considered viable and who were referred to palliative care programs. Clinical and biologic prognostic factors included in the PaP score were assessed at study entry. The Confusion Assessment Method criteria were applied to screen patients presenting with delirium. Survival times were measured from time of enrollment and death taken as an outcome. Survival curves were traced with the Kaplan-Meier method and comparison were based on log rank tests. RESULTS: Delirium was found in 109 cases among 393 consecutive patients (27.7%). The diagnosis of delirium was independently associated with male gender, central nervous system metastases, lower performance status, worse clinical prediction of survival, and progestational treatment. The survival curve of patients with delirium was significantly different from the nondelirious patients curve (log rank, 31.6, P < 0.0001). The median survival time was 21 days (95% confidence interval [CI], 16-27) for the delirious patients and 39 days (95% CI 33-49) for the others. Multivariate analysis showed that the diagnosis of delirium and PaP score were independently associated with prognosis. CONCLUSIONS: The diagnosis of delirium significantly worsens life expectancy prognosticated with the PaP score. By using the PaP score together with the assessment of cognitive status, physicians can correctly predict patients 30-day survival in greater than 70% of cases.     

Clinician prediction of survival versus the Palliative Prognostic Score: Which approach is more accurate?

BackgroundClinician prediction of survival (CPS) has low accuracy in the advanced cancer setting, raising the need for prediction models such as the palliative prognostic (PaP) score that includes a transformed CPS (PaP-CPS) and five clinical/laboratory variables (PaP-without CPS). However, it is unclear if the PaP score is more accurate than PaP-CPS, and whether PaP-CPS helps to improve the accuracy of PaP score. We compared the accuracy among PaP-CPS, PaP-without CPS and PaP-total score in patients with advanced cancer.Patients and methodsIn this prospective study, PaP score was documented in hospitalised patients seen by palliative care. We compared the discrimination of PaP-CPS versus PaP-total and PaP-without CPS versus PaP-total using four indices: concordance statistics, area under the receiver-operating characteristics curve (AUC), net reclassification index and integrated discrimination improvement for 30-day survival and 100-day survival.ResultsA total of 216 patients were enrolled with a median survival of 109 d (95% confidence interval [CI] 71–133 d). The AUC for 30-day survival was 0.57 (95% CI 0.47–0.67) for PaP-CPS, 0.78 (95% CI 0.7–0.87) for PaP-without CPS, and 0.73 (95% CI 0.64–0.82) for PaP-total score. PaP-total was significantly more accurate than PaP-CPS according to all four indices for both 30-day and 100-day survival (P < 0.001). PaP-without CPS was significantly more accurate than PaP-total for 30-day survival (P < 0.05).ConclusionWe found that PaP score was more accurate than CPS, and the addition of CPS to the prognostic model reduced its accuracy. This study highlights the limitations of clinical gestalt and the need to use objective prognostic factors and models for survival prediction.     

Prospective comparison of prognostic scores in palliative care cancer populations

Purpose.

Predicting prognosis in advanced cancer aids physicians in clinical decision making and can help patients and their families to prepare for the time ahead.

Materials and Methods.

This multicenter, observational, prospective, nonrandomized population-based study evaluated life span prediction of four prognostic scores used in palliative care: the original Palliative Prognostic Score (PaP Score), a variant of PaP Score including delirium (D-PaP Score), the Palliative Performance Scale, and the Palliative Prognostic Index.

Results.

A total of 549 patients were enrolled onto the study. Median survival of the entire group was 22 days (95% confidence intervals [95% CI] = 19–24). All four prognostic models discriminated well between groups of patients with different survival probabilities. Log-rank tests were all highly significant (p < .0001). The PaP and D-PaP scores were the most accurate, with a C index of 0.72 (95% CI = 0.70–0.73) and 0.73 (95% CI = 0.71–0.74), respectively.

Conclusion.

It can be confirmed that all four prognostic scores used in palliative care studies accurately identify classes of patients with different survival probabilities. The PaP Score has been extensively validated and shows high accuracy and reproducibility in different settings.     

Survival prediction for terminally ill cancer patients: revision of the palliative prognostic score with incorporation of delirium

Purpose.

An existing and validated palliative prognostic (PaP) score predicts survival in terminally ill cancer patients based on dyspnea, anorexia, Karnofsky performance status score, clinical prediction of survival, total WBC, and lymphocyte percentage. The PaP score assigns patients to three different risk groups according to a 30-day survival probability—group A, >70%; group B, 30%–70%; group C, <30%. The impact of delirium is known but was not incorporated into the PaP score.

Materials and Methods.

Our aim was to incorporate information on delirium into the PaP score based on a retrospective series of 361 terminally ill cancer patients. We followed the approach of “validation by calibration,” proposed by van Houwelingen and later adapted by Miceli for achieving score revision with inclusion of a new variable. The discriminating performance of the scores was estimated using the K statistic.

Results.

The prognostic contribution of delirium was confirmed as statistically significant (p < .001) and the variable was accordingly incorporated into the PaP score (D-PaP score). Following this revision, 30-day survival estimates in groups A, B, and C were 83%, 50%, and 9% for the D-PaP score and 87%, 51%, and 16% for the PaP score, respectively. The overall performance of the D-PaP score was better than that of the PaP score.

Conclusion.

The revision of the PaP score was carried out by modifying the cutoff values used for prognostic grouping without, however, affecting the partial scores of the original tool. The performance of the D-PaP score was better than that of the PaP score and its key feature of simplicity was maintained.     

Second-line chemotherapy for patients with advanced gastric cancer: who may benefit?

No established second-line chemotherapy is available for patients with advanced gastric cancer failing to respond or progressing to first-line chemotherapy. However, 20-40% of these patients commonly receive second-line chemotherapy. We evaluated the influence of clinico-pathologic factors on the survival of 175 advanced gastric cancer patients, who received second-line chemotherapy at three oncology departments. Univariate and multivariate analyses found five factors which were independently associated with poor overall survival: performance status 2 (hazard ratio (HR), 1.79; 95% CI, 1.16-2.77; P=0.008), haemoglobin 50 ng ml(-1) (HR, 1.86; 95% CI, 1.21-2.88; P=0.004), the presence of greater than or equal to three metastatic sites of disease (HR, 1.72; 95% CI, 1.16-2.53; P=0.006), and time-to-progression under first-line chemotherapy 相似文献   

A phase II study of S-1 monotherapy administered for 2 weeks of a 3-week cycle in advanced gastric cancer patients with poor performance status

Systemic chemotherapy for gastric cancer is often associated with treatment-related toxicity, which is particularly severe in patients with a poor performance status. In this paper, we describe the first study to evaluate S-1 monotherapy as an option for advanced gastric cancer patients who are not candidates for combination chemotherapy due to poor clinical condition. Fifty-two patients with Eastern Cooperative Oncology Group (ECOG) performance scale 2-3, whose general condition had made use of combination chemotherapy impossible, were enrolled. S-1 was administered to 30 patients as second- or third-line therapy. The initial dose of S-1 was 35 mg m(-2), administered b.i.d for 14 days every 3 weeks. With a median follow-up period of 33 weeks, the median progression-free survival, and overall survival were 11 weeks (95% CI, 8-14) and 33 weeks (95% CI, 19-47), respectively. The overall 1-year survival rate was 29% by intent-to-treat analysis. The overall response rate was 12% (95% CI, 3-21), and the percentage of stable disease was 35%, resulting in the disease control rate of 47% (95% CI, 32-60). Significant drug-related toxicity included grade 3 diarrhoea (14%), anorexia (14%), fatigue (10%), neutropenia (10%), and leucopenia (6%). In conclusion, this study indicated the modest activity of S-1 in gastric cancer patients with poor performance status.     

Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer

BACKGROUND: Recently, it was shown that an inflammation-based prognostic score, the Glasgow Prognostic Score (GPS), provides additional prognostic information in patients with advanced cancer. The objective of the current study was to examine the value of the GPS compared with established scoring systems in predicting cancer-specific survival in patients with metastatic renal cancer. METHODS: One hundred nineteen patients who underwent immunotherapy for metastatic renal cancer were recruited. The Memorial Sloan-Kettering Cancer Center (MSKCC) score and the Metastatic Renal Carcinoma Comprehensive Prognostic System (MRCCPS) score were calculated as described previously. Patients who had both an elevated C-reactive protein level (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients who had only 1 of those 2 biochemical abnormalities were allocated a GPS of 1. Patients who had neither abnormality were allocated a GPS of 0. RESULTS: On multivariate analysis of significant individual factors, only calcium (hazard ratio [HR], 3.21; 95% confidence interval [95% CI], 1.51-6.83; P = .002), white cell count (HR, 1.66; 95% CI, 1.17-2.35; P = .004), albumin (HR, 2.63; 95% CI, 1.38-5.03; P = .003), and C-reactive protein (HR, 2.85; 95% CI; 1.49-5.45; P = .002) were associated independently with cancer-specific survival. On multivariate analysis of the different scoring systems, the MSKCC (HR, 1.88; 95% CI, 1.22-2.88; P = .004), the MRCCPS (HR, 1.42; 95% CI, 0.97-2.09; P = .071), and the GPS (HR, 2.35; 95% CI, 1.51-3.67; P < .001) were associated independently with cancer-specific survival. CONCLUSIONS: An inflammation-based prognostic score (GPS) predicted survival independent of established scoring systems in patients with metastatic renal cancer.     

Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients with advanced cancer. The aim of the present study was to examine whether an inflammation-based prognostic score (Glasgow Prognostic score, GPS) was associated with survival, in patients with inoperable gastro-oesophageal cancer. Patients diagnosed with inoperable gastro-oesophageal carcinoma and who had measurement of albumin and C-reactive protein concentrations, at the time of diagnosis, were studied (n=258). Clinical information was obtained from a gastro-oesophageal cancer database and analysis of the case notes. Patients with both an elevated C-reactive protein (>10 mg l(-1)) and hypoalbuminaemia (<35 g l(-1)) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. On multivariate survival analysis, age (hazard ratio (HR) 1.22, 95% CI 1.02-1.46, P<0.05), stage (HR 1.55, 95% CI 1.30-1.83, P<0.001), the GPS (HR 1.51, 95% CI 1.22-1.86, P<0.001) and treatment (HR 2.53, 95% CI 1.80-3.56, P<0.001) were significant independent predictors of cancer survival. A 12-month cancer-specific survival in patients with stage I/II disease receiving active treatment was 67 and 60% for a GPS of 0 and 1, respectively. For stage III/IV disease, 12 months cancer-specific survival was 57, 25 and 12% for a GPS of 0, 1 and 2, respectively. In the present study, the GPS predicted cancer-specific survival, independent of stage and treatment received, in patients with inoperable gastro-oesophageal cancer. Moreover, the GPS may be used in combination with conventional staging techniques to improve the prediction of survival in patients with inoperable gastro-oesophageal cancer.     

Survival prediction for advanced cancer patients in the real world: A comparison of the Palliative Prognostic Score,Delirium-Palliative Prognostic Score,Palliative Prognostic Index and modified Prognosis in Palliative Care Study predictor model

PurposeThe aim of this study was to investigate the feasibility and accuracy of the Palliative Prognostic Score (PaP score), Delirium-Palliative Prognostic Score (D-PaP score), Palliative Prognostic Index (PPI) and modified Prognosis in Palliative Care Study predictor model (PiPS model).Patients and methodsThis multicentre prospective cohort study involved 58 palliative care services, including 19 hospital palliative care teams, 16 palliative care units and 23 home palliative care services, in Japan from September 2012 to April 2014. Analyses were performed involving four patient groups: those treated by palliative care teams, those in palliative care units, those at home and those receiving chemotherapy.ResultsWe recruited 2426 participants, and 2361 patients were finally analysed. Risk groups based on these instruments successfully identified patients with different survival profiles in all groups. The feasibility of PPI and modified PiPS-A was more than 90% in all groups, followed by PaP and D-PaP scores; modified PiPS-B had the lowest feasibility. The accuracy of prognostic scores was ⩾69% in all groups and the difference was within 13%, while c-statistics were significantly lower with the PPI than PaP and D-PaP scores.ConclusionThe PaP score, D-PaP score, PPI and modified PiPS model provided distinct survival groups for patients in the three palliative care settings and those receiving chemotherapy. The PPI seems to be suitable for routine clinical use for situations where rough estimates of prognosis are sufficient and/or patients do not want invasive procedure. If clinicians can address more items, the modified PiPS-A would be a non-invasive alternative. In cases where blood samples are available or those requiring more accurate prediction, the PaP and D-PaP scores and modified PiPS-B would be more appropriate.     

Paclitaxel and leucovorin-modulated infusional 5-fluorouracil combination chemotherapy for metastatic gastric cancer

As no standard chemotherapy regimen has been established for advanced gastric cancer, this study sought to evaluate the efficacy and safety of combination chemotherapy that included paclitaxel and leucovorin (LV)-modulated infusional 5-fluorouracil (5-FU) in metastatic gastric cancer. Patients received a three-hour infusion of 175 mg/m2 of paclitaxel on day 1. A bolus of 20 mg/m2 of LV was then administered, followed by a 24-h infusion of 1,000 mg/m2 of 5-FU on days 1 through 3. The treatment cycle was re-peated every 3 weeks until disease progression. Response evaluation was performed according to the RECIST criteria, with toxicity determined by NCI-CTC (version 2.0). A total of 66 patients, including 21 (31.8%) with a history of prior chemotherapy, were enrolled. Fifteen (71.4%) of the 21 patients with prior chemotherapy received prolonged infusional 5-FU. In the 56 evaluable patients (37 in the chemotherapy-na?ve group and 19 in the prior chemotherapy group), tumor responses according to prior exposure to chemotherapy were as follows: 17 (45.9%) partial response (PR), 6 (16.2%) stable disease (SD) and 14 (37.8%) progressive disease (PD) in the chemotherapy-na?ve group; 1 (7.1%) complete response, 3 (15.8%) PRs, 8 (42.1%) SDs and 7 (36.8%) PDs in the prior chemotherapy group. The overall median response duration was 20 weeks (range, 8-61 weeks), with a median progression-free survival of 20 weeks [95% confidence interval (CI), 13.4-26.6 weeks] and 12 weeks (95% CI, 5.7-18.3 weeks) in the chemotherapy-na?ve and prior chemotherapy groups, respectively. The median overall survival was 48 weeks (95% CI, 38-58 weeks) in the chemotherapy-na?ve group and 28 weeks (95% CI, 22-34 weeks) in the prior chemotherapy group. The most frequent grade III/IV toxicity was neutro-penia. Non-hematological toxicity of grade III/IV was rare. Paclitaxel in combination with 5-FU/LV is clinically beneficial for patients with advanced gastric cancer and is a feasible salvage regimen for 5-FU-refractory gastric cancer patients.     

The role of the surgeon in whether patients with lymph node-positive colon cancer see a medical oncologist

BACKGROUND: Chemotherapy improves survival for patients with stage III colon cancer, but some older patients with lymph node-positive colon cancer do not see a medical oncologist and, thus, do not receive adjuvant chemotherapy. METHODS: To evaluate the role of the surgeon in determining referrals to medical oncology among patients with stage III colon cancer, the authors conducted a retrospective cohort study of 6158 patients aged >or=66 years who were diagnosed with stage III colon cancer from 1992 through 1999 by using the Surveillance, Epidemiology, and End Results-Medicare linked database. Multilevel analysis was used to simultaneously model variations in patients' seeing a medical oncologist at the patient and surgeon levels. RESULTS: Twenty-one percent of the total variance in seeing a medical oncologist was attributable to the surgeon after adjusting for available patient, tumor, and surgeon characteristics. The individual surgeon characteristics that significantly predicted whether the patient saw a medical oncologist were year since graduation (20 years; hazard ratio [HR], 1.60; 95% confidence interval [95% CI], 1.19-2.16), practicing in a teaching hospital (yes vs. no: HR; 1.30; 95% CI, 1.07-1.58), and volume of patients with colon cancer (<30 patients vs >or=121 patients; HR, 0.66; 95% CI, 0.46-0.94). Surgeon sex, race, board certification, and type of practice were not independent predictors of medical oncology referral. CONCLUSIONS: Surgeons accounted for approximately 20% of the variation in patients seeing a medical oncologist. Interventions at the level of the surgeon may be appropriate to improve the care of patients with colon cancer.     

Long-term outcomes and prognostic factors of patients with advanced gastric cancer treated with S-1 plus cisplatin combination chemotherapy as a first-line treatment

Background

The long-term outcomes of advanced gastric cancer (AGC) patients treated with S-1 plus cisplatin (SP) combination chemotherapy remain unclear. Therefore, we sought to evaluate these outcomes to identify the prognostic factors affecting patient survival.

Methods

We retrospectively analyzed 153 AGC patients treated with SP at a single institution between January 2005 and July 2011.

Results

Median overall survival (OS) was 15.0 months [95 % confidence interval (CI), 12.5–17.9 months]. Three independent prognostic factors affecting poor survival were identified: performance status (PS) ≥ 1 [hazard ratio (HR) = 2.39, 95 % CI, 1.58–3.62); >1 metastatic site (HR = 1.57, 95 % CI, 1.10–2.26], and elevated alkaline phosphatase levels (HR = 1.70, 95 % CI, 1.16–2.49). A simple prognostic index was generated using three risk groups: good (no risk factor), moderate (one or two risk factors), and poor (three risk factors). The median OS for good-, moderate-, and poor-risk groups was 28.6, 14.8, and 7.3 months, respectively (log-rank test; P < 0.0001). Among the twelve 3-year survivors, 9 (75 %) had a PS of 0 and 8 (67 %) had only one metastatic site.

Conclusions

Three prognostic factors were identified in AGC patients treated with SP. Using a simple prognostic index, the patients were divided into three risk groups, in which the survival differences were markedly significant, suggesting that patients with good PS and only one metastatic site may have a higher chance of long-term survival than those with poor PS and multiple metastatic sites.     

替吉奥治疗晚期或复发性胃癌的疗效观察

目的分析晚期或复发性胃癌患者应用替吉奥单药治疗后的疗效、毒副反应。方法 28例患者根据体表面积给予替吉奥胶囊治疗,并评价患者的疾病控制率、无进展生存期和生存期。结果替吉奥对晚期胃癌和复发性胃癌的疾病控制率为39.3%。中位无进展生存期为4.0个月（95%CI,2.1~5.9个月）,晚期胃癌患者的中位无进展生存期为5.9个月（95%CI,3.1~8.5个月）,复发性胃癌的PFS中位值为3.1个月（95%CI,1.9~4.6个月）。中位生存期为10.5个月（95%CI,6.2~16.1个月）,晚期胃癌患者的中位生存期为10.0个月（95%CI,4.7~14.9个月）,复发性胃癌患者的中位生存期为14.2个月（95%CI,4.5~24.1个月）。Ⅲ、Ⅳ度毒副反应的发生率为10.7%。结论替吉奥治疗晚期或复发性胃癌安全有效,能延长患者生存期。     

Outcomes in 144 Patients With Colorectal Cancer Treated in a Phase I Clinic: The MD Anderson Cancer Center Experience

BackgroundPatients with advanced colorectal cancer have a poor prognosis once standard therapies fail. This retrospective study presents the characteristics and outcomes in 144 patients treated in phase I clinical trials.MethodsWe retrospectively reviewed the clinical outcomes in 144 consecutive patients with colorectal cancer referred to the phase I clinic at MD Anderson.ResultsMedian age was 60 years (range, 35-86 years). The median number of previous systemic therapies was 4 (range, 1-7). The median PFS with the last line of conventional systemic treatment was 12.3 weeks (95% confidence interval [CI], 11.0-14.4); the median PFS of the best phase I treatment was shorter at 8.1 weeks (95% CI, 7.9-8.7 weeks; log-rank test, P < .0001). In the multivariate analysis that included the RMH score, sex (male vs. female, P = .02; hazard ratio [HR], 1.57), hemoglobin (< 10.5 vs. ≥ 10.5 g/dL; P = .03; HR 1.79), and the RMH score (2-3 vs. 0-1; P < .003; HR, 1.85) were significant predictors of poor survival. Conclusion: The PFS of patients with colorectal cancer in phase I treatment was shorter than it was on their last line of conventional systemic treatment. Multivariate analysis confirmed the value of the RMH score for predicting overall survival in patients with colorectal cancer enrolled in phase I studies.     

Capecitabine and doxorubicin combination chemotherapy as salvage therapy in pretreated advanced gastric cancer

Purpose The aim of this study was to evaluate the activity and the safety of a combination regimen of capecitabine and doxorubicin as salvage chemotherapy in advanced gastric cancer patients who had undergone one or two prior chemotherapy regimens. Methods Patients received capecitabine, 2,500 mg/m²/day PO for 14 days (D1–14) and doxorubicin, 30 mg/m² IV on day 1 every 3 weeks until disease progression. The response was evaluated according to RECIST criteria, and the toxicity was evaluated by NCI-CTC (version 2.0). Results Forty-five patients were enrolled. Twenty-six patients were treated as second-line chemotherapy and the remaining patients as third-line chemotherapy. A total of 152 cycles of chemotherapy (median 2, range 1–12) were administered. Median dose intensities of capecitabine and doxorubicin were 11,326 and 9.6 mg/m²/week, respectively. The overall response rate was 6.7% (95% CI, 4.1–12.5%) and the disease control rate was 46.7% (95% CI, 28.6–87.1%) according to an intent-to-treat analysis. The median progression-free survival was 11.3 weeks (95% CI, 5.6–16.7 weeks). The median overall survival was 29.1 weeks (95% CI, 18.3–39.9 weeks) with one-year survival rate of 24%. Severe (grade III/IV) hematologic and non-hematologic toxicity was uncommon and included nausea/vomiting in five (11.1%), neutropenia in two (4.4%), anemia in one (2.2%), and hand-foot syndrome in one patient (2.2%). Conclusions The combination of capecitabine and doxorubicin is a feasible salvage regimen in advanced pre-treated gastric cancer.     

Comparison of the prognostic value of selected markers of the systemic inflammatory response in patients with colorectal cancer

There is increasing evidence that the presence of a systemic inflammatory response plays an important role in predicting survival in patients with colorectal cancer. However, it is not clear what components of the systemic inflammatory response best predict survival. The aim of the present study was to compare the prognostic value of an inflammation-based prognostic score (modified Glasgow Prognostic Score (Mgps) 0=C-reactive protein <10 mg l(-1), 1=C-reactive protein >10 mg l(-1), and 2=C-reactive protein >10 mg l(-1) and albumin<35 g l(-1)) with that of components of the white cell count (neutrophils, lymphocytes, monocytes and platelets using standard thresholds) in patients with colorectal cancer. Two patient groups were studied: 149 patients who underwent potentially curative resection for colorectal cancer and 84 patients who had synchronous unresectable liver metastases. In those patients who underwent potentially curative resection the minimum follow-up was 36 months and 20 patients died of their cancer. On multivariate survival analysis only TNM stage (HR 3.75, 95% CI 1.54-9.17, P=0.004), monocyte count (HR 3.79, 95% CI 1.29-11.12, P=0.015) and mGPS (HR 2.21, 95% CI 1.11-4.41, P=0.024) were independently associated with cancer-specific survival. In patients with synchronous unresectable liver metastases the minimum follow-up was 6 months and 71 patients died of their cancer. On multivariate survival analysis only single liver metastasis >5 cm (HR 1.78, 95% CI 0.99-3.21, P=0.054), extra-hepatic disease (HR 2.09, 95% CI 1.05-4.17, P=0.036), chemotherapy treatment (HR 2.40, 95% CI 1.82-3.17, P<0.001) and mGPS (HR 1.44, 95% CI 1.01-2.04, P=0.043) were independently associated with cancer-specific survival. In summary, markers of the systemic inflammatory response are associated with poor outcome in patients with either primary operable or synchronous unresectable colorectal cancer. An acute-phase protein-based prognostic score, the mGPS, appears to be a superior predictor of survival compared with the cellular components of the systemic inflammatory response.     

Phase II Study of Continued Trastuzumab Plus Irinotecan in Patients with HER2-positive Gastric Cancer Previously Treated with Trastuzumab (HGCSG 1201)

BackgroundThe efficacy of irinotecan plus continuous trastuzumab beyond progression in patients with gastric cancer previously treated with trastuzumab plus standard first-line chemotherapy has not been reported.MethodsPatients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer who were previously treated with trastuzumab received trastuzumab every 3 weeks and irinotecan every 2 weeks. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), 6-month survival rates, safety, and subgroup analysis by HER2 status.ResultsSixteen patients were enrolled in a 3-year pre-planned registration period. This study was prematurely closed due to poor patient accrual. The ORR and disease control rate were 6.7% (95% CI, 0.2-32.0) and 53.3% (95% CI, 26.6-78.7). The median PFS and overall survival (OS) were 2.4 months (95% CI, 0.0-5.2) and 9.7 months (95% CI, 8.2-11.2), respectively. The most frequently reported grades 3-4 adverse events were neutropenia (40%), anemia (27%), anorexia (33%), and fatigue (33%).ConclusionWith only 16 patients enrolled, the present study has very low power to detect any clinical benefit of trastuzumab plus irinotecan beyond disease progression in patients with HER2-positive advanced gastric cancer who previously received trastuzumab.Trial Identifier: UMIN000007636.     

Weekly short infusion of taxotere at a 4 week cycle in Chinese patients with advanced NSCLC who have failed or relapsed after the frontline platinum-based non-taxane chemotherapy--a Phase II trial

BACKGROUND: This Phase II study was conducted to evaluate the efficacy and toxicity of weekly docetaxel at a 4 week cycle in second-line therapy for patients with advanced non-small cell lung cancer (NSCLC) who failed to respond or relapsed after the frontline platinum-based, non-taxane regimen. METHODS: Patients with histologically confirmed and progressive NSCLC after one platinum-based, non-taxane regimen were eligible for this study. Performance status of 0-2 and adequate organ function were required. Patients were treated with docetaxel 40 mg/m(2)/week for three consecutive weeks then following 1 week of rest. Cycles were repeated every 4 weeks for a maximum total of six cycles. Docetaxel was administered intravenously for 30 min with dexamethasone premedication. RESULTS: Fifty-three patients were eligible for this study. Hematologic toxicity was very mild and with the major toxicity of anemia. Non-hematologic toxicities were modest, Grades 3-4 mucositis, diarrhea and peripheral neuropathy occurred in 6-13% of patients and caused dose modifications. Fatigue (48%) was common but not severe with only 6% of Grades 3-4 toxicity. The overall response rate (ORR) was 13% [95% confidence interval (CI), 3.9-23%]. The median survival time (MST) for all patients was 25.0 weeks (95% CI, 12.7-37.3), and the 1 year survival was 31% (95% CI, 17-58%). For patients with PS 0-1, MST was 29.7 weeks and 1 year survival was 36%. CONCLUSIONS: Weekly docetaxel appeared to be well tolerated as second-line therapy for patients with NSCLC. The efficacy for this regimen was comparable with the standard 3 week schedule but hematologic toxicity was markedly reduced. A schedule of three consecutive weeks, with a 1 week break, may diminish the frequency of fatigue and diarrhea when compared with a schedule of six consecutive weeks.