Addition Of Consolidation Chemotherapy Research Articles

Efficacy and safety of consolidation chemotherapy during the resting period in patients with local advanced rectal cancer

It remains controversial as to whether a long interval between neoadjuvant chemoradiotherapy (NCRT) and surgery may provide clinical benefits for patients with local advanced rectal cancer (LARC). The addition of consolidation chemotherapy during the resting period was recently considered as a treatment option. The present study aimed to verify the efficacy and safety of consolidation chemotherapy during the resting period in patients with LARC. A total of 156 patients with local advanced stage T3-4N0-2 rectal cancer were enrolled between January 2010 and July 2016. Patients were divided into two groups, those who received consolidation chemotherapy prior to surgery (n=76) and the control group who did not (n=80). Multivariate logistic regression and the Kaplan-Meier method were used to explore the predictors of pathological complete response (pCR) and survival. The demographic and tumor characteristics were comparable between the two groups. The consolidation group yielded significantly higher pCR and near pCR rates compared with the control group (P=0.015). Patients in the consolidation group who also underwent standard adjuvant chemotherapy displayed improved 3-year disease-free survival (DFS) compared with the control group (P=0.036). Notably, the addition of consolidation chemotherapy between NCRT and surgery did not significantly increase the incidence of surgical complications and grade 3 or 4 toxicities when compared with the control group. Consolidation chemotherapy was associated with increased pCR/near pCR rates and improved 3-year DFS, and displayed a manageable safety profile. The present study provided primary evidence for the efficacy and safety of consolidation chemotherapy in LARC. Further prospective studies are warranted in the future to verify these results.

Is Consolidation Chemotherapy after Concurrent Chemo-Radiotherapy Beneficial for Patients with Locally Advanced Non–Small-Cell Lung Cancer?: A Pooled Analysis of the Literature

The purpose of this study was to evaluate whether consolidation chemotherapy (CCT) after concurrent chemo-radiotherapy is beneficial for patients with locally advanced non-small-cell lung cancer (LA-NSCLC). We systematically searched PubMed for phase II/III trials published before December 31, 2011, examining survival of LA-NSCLC treated with concurrent chemo-radiotherapy. Median overall survival and other study characteristics were collected from each study and pooled. We extracted log-transformed hazards and standard errors under the assumption that survival follows an exponential distribution, and computed a pooled median overall survival and a 95% confidence interval (CI) using random-effects model. Collected trial arms were categorized as having CCT or not having it, CCT+ and CCT-, respectively. Forty-one studies were identified including seven phase III studies and 34 phase II studies with 45 arms (CCT+: 25; CCT-: 20). Clinical data were comparable for clinical stage, performance status, cancer histology, sex, and median age between the two groups. There was no statistical difference in pooled mOS between CCT+ (19.0 month; 95% CI, 17.3-21.0) and CCT- (17.9 month; 95% CI, 16.1-19.9). Predicted hazard ratio of CCT+ to CCT- was 0.94 (95% CI, 0.81-1.09; p = 0.40). There were no differences between the two groups with regard to grade 3-5 toxicities in pneumonitis, esophagitis, and neutropenia. These models estimated that addition of CCT could not lead to significant survival prolongation or risk reduction in death for LA-NSCLC patients. The pooled analysis based on a publication basis failed to provide evidence that CCT yields significant survival benefit for LA-NSCLC.

Is consolidation chemotherapy after concurrent chemoradiotherapy beneficial for locally advanced non-small cell lung cancer? A pooled analysis of the literature.

7000 Background: There is a growing interest on the efficacy of maintenance chemotherapy to metastatic non-small cell lung cancer (NSCLC) and adjuvant chemotherapy to early stage NSCLC. However, the role of consolidation chemotherapy (CCT) after concurrent chemo-radiotherapy in locally advanced NSCLC is undetermined. Methods: We systematically searched PubMed for phase II/III trials examining survival of locally-advanced NSCLC treated with concurrent chemo-radiotherapy between January 1, 1995 and October 31, 2011. Median overall survival (mOS) and corresponding 95% confidence interval (CI) were collected from each study and pooled. We extracted log-transformated hazards and its standard errors under the assumption that survival follows an exponential distribution, and computed a pooled mOS and its 95% CI using random-effect model. Collected trial arms were divided into two groups by the presence of CCT: Arm with CCT (CCT+) and without CCT (CCT-). Results: Forty-five studies were identified including 9 phase III studies and 36 phase II studies with 51 arms (CCT+: 29, CCT-: 22). Clinical data were comparable in clinical stage, performance status, cancer histology, gender, and median age between the two groups. I2 values for assessing heterogeneity were 15.3, 9.1 and 24.2% in overall, CCT+ and CCT- studies, respectively. There was no statistical difference in pooled mOS between CCT+ (18.5 month, 95%CI: 16.7-20.5) vs CCT- (18.1 month, 95%CI: 16.5-20.2). In regard to the ≥ grade 3 toxicities in pneumonitis, esophagitis, and neutropenia, there was no difference between the two groups throughout the whole treatment courses. In random effect models, predicted hazard ratio of CCT+ to CCT- was 0.98 (95%CI: 0.8-1.13, p=0.7574). These models estimated that addition of CCT could not yield more than 3 months of survival prolongation for patients with locally advanced NCSLC. Conclusions: The pooled analysis on publication basis failed to provide evidence that consolidation chemotherapy yields significant survival benefit for locally advanced NSCLC.

Locally advanced non–small cell lung cancer: What is the optimal concurrent chemoradiation regimen?

The optimal chemoradiation regimen for patients with locally advanced non-small cell lung cancer (NSCLC) has yet to be defined. Disease and patient heterogeneity prevent a "one size fits all" approach to treatment. Concurrent chemoradiation up front is the definitive strategy for patients with unresectable stage III NSCLC; the addition of consolidation chemotherapy following definitive treatment has produced conflicting results with respect to overall survival. Biologic therapies have yet to show value as add-on treatment to chemoradiation.

Will Future Progress in Non–Small-Cell Lung Cancer Be Step by Step … or by Leaps and Bounds?

“We cannot sit and wait for the promise of tomorrow so long as stepwise progress can be made with the tools at hand today.” In terms of lung cancer therapy, these words of Dr Howard Skipper from 1979 seem to apply just as much today as they did a quarter of a century ago. Before 1980, the standard of care for locally advanced/unresectable non– small-cell lung cancer (LA-NSCLC) was definitive radiation therapy (RT) alone. However, the 5-year survival rate was disappointingly low, at only 5%. The treatment paradigm began to shift after a landmark trial by the Cancer and Leukemia Group B (CALGB 84-33) demonstrated that induction chemotherapy (with two cycles of cisplatin and vinblastine) followed by RT significantly improved survival compared with RT alone. Yet, the results with sequential chemotherapy followed by RT in CALGB 84-33 seemed too good to be true. There was almost a “triple jump” improvement in the 5-year survival from 6% with RT alone to 17% with sequential therapies. Indeed, two subsequent randomized trials utilizing the same regimen as CALGB 84-33 (with substantially more patients) demonstrated more modest long-term survival rates of 8% to 10%. The next incremental gain in LA-NSCLC came from the use of concurrent rather than sequential chemotherapy and RT. In 1999, Furuse et al reported in the Journal of Clinical Oncology the results of a randomized trial with 320 patients, comparing sequential chemotherapy (mitomycin, vindesine, and cisplatin) followed by RT (56 Gy) versus concurrent chemoradiotherapy. They found a statistically significant improvement in 5-year survival of 16% for concurrent chemoradiotherapy compared with 9% for sequential therapies (P .01). In another randomized trial with more than 600 patients, Radiation Therapy Oncology Group (RTOG) trial 94-10, Curran et al reported remarkably similar superior results of once-a-day RT (63 Gy) concurrent with chemotherapy over the same therapies delivered sequentially. Zatloukal et al also performed a randomized phase II trial favoring concurrent therapy. Patterns of failure data suggest that the benefit of concurrent chemoradiotherapy is due to a synergistic effect that leads to an improvement in local, rather than distant, control. In this issue of the Journal, Fournel et al add yet another study corroborating the clinical benefit of concurrent over sequential chemoradiotherapy. In this phase III trial, 212 patients were randomly assigned between induction chemotherapy with cisplatin and vinorelbine followed by RT (66 Gy), compared with the same RT concurrent with cisplatin and etoposide followed by consolidation therapy with cisplatin and vinorelbine. While not statistically significant, they report potentially clinically meaningful differences in the median and 4-year survival rates, favoring the concurrent arm (16.3 v 14.5 months and 21% v 14%, respectively). The key reason for the borderline result was the lack of adequate statistical power in this study to reject the null hypothesis. According to their study design, with a calculated sample size of 210 patients, Fournel et al only had the ability to detect an improvement in 2-year survival from 20% in the sequential arm to 35% in the concurrent arm. This relative improvement of 75% was simply too high a bar, too great a leap, and did not follow the general rule of “stepwise” improvements that one would expect in this setting. Moreover, unlike RTOG 94-10, this trial was confounded by the addition of consolidation chemotherapy in the experimental arm. Fortunately, this was not the first trial on this subject, or some may have incorrectly concluded that concurrent therapy is no better than sequential treatments. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 25 SEPTEMBER 1 2005

Current Controversies: Which Patients With Acute Myeloid Leukaemia Should Receive A Bone Marrow Transplantation? – An Adult Treater's View

Current Controversies: Which Patients With Acute Myeloid Leukaemia Should Receive A Bone Marrow Transplantation? – An Adult Treater's View

Carboplatin plus paclitaxel and sequential radiation followed by consolidation carboplatin and paclitaxel in patients with previously untreated locally advanced NSCLC: A Hoosier Oncology Group (HOG) phase II study

Chemoradiation is standard treatment for patients with unresectable locally advanced non-small cell lung cancer (NSCLC). However, local and distant relapse rates remain high. It has been postulated that the addition of consolidation chemotherapy might further decrease the systemic relapse rate. We performed this phase II study to evaluate the toxicities and activity of two cycles of paclitaxel and carboplatin administered prior to and following thoracic radiation in patients with locally advanced, inoperable NSCLC. From April to December 1997, 25 patients were entered on study. Twenty-three patients were eligible and received paclitaxel 225 mg/m 2 intravenously over 3 h followed by carboplatin at an AUC (6) on days 1 and 22. Radiation consisted of 60 Gy given over 6 weeks beginning on day 43. Patients with non-progressive disease received two additional cycles of consolidation carboplatin and paclitaxel. Four of 23 patients progressed during induction chemotherapy. There were seven PR's and 11 had SD after induction chemotherapy. Following radiation, the response changed to 11 PR, four SD, and three had progressive disease. Of the 15 patients eligible to receive consolidation chemotherapy, three were excluded due to a poor performance status. Twelve patients were treated with consolidation chemotherapy with further improvement in two patients (SD to PR, PR to CR). All 12 patients who received consolidation chemotherapy developed grade 3 or 4 neutropenia, including three patients with neutropenic fever. The overall response rate was 52.1%. The median survival, 1-, and 2-year survival was 10.5 months, 45, and 17%, respectively. In conclusion, consolidation chemotherapy was associated with significant hematologic toxicity without an obvious improvement in survival in comparison to other studies utilizing chemoradiation alone.