Standard Adjuvant Treatment For Stage Research Articles

Impact of relative dose intensity of oxaliplatin in adjuvant therapy among stage III colon cancer patients on early recurrence: a retrospective cohort study

BackgroundOxaliplatin-based therapy with FOLFOX-4 or CAPOX administered over 6 months remains the standard adjuvant treatment for stage III colon cancer (CC) patients. However, many patients experience dose reduction or early termination of chemotherapy due to oxaliplatin toxicity, which may increase the risk of early recurrence. The objective of this study was to analyze the relationship between the relative dose intensity of oxaliplatin (RDI-O) and early recurrence among stage III CC patients.MethodsThe study included 365 patients treated at five oncology centers in Poland between 2000 and 2014. Survival analysis was performed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazard model; multivariate analysis was performed with the stepwise forward approach. For all analyses the α level of 0.05 was employed.ResultsThe median follow-up was 51.8 months (range 8.2–115.1). Early recurrence < 36 months after surgery occurred in 130 patients (37.8%). In this group 51 (39.2%) and 87 (66.9%) of patients were low and high-risk, respectively. Receipt < 60% of RDI-O was associated with early recurrence within 18 months after surgery (OR = 2.05; 95%CI: 1.18–3.51; p = 0.010), especially in low-risk group (HR = 1.56 (95%CI: 0.96–2.53), p = 0.07). In the multivariate analysis early recurrence was correlated with grade (OR = 2.47; 95% CI: 1.25–4.8; p = 0.008), pN (OR = 2.63; 95% CI: 1.55–4.54; p < 0.001), the number of lymph nodes harvested (OR = 0.51; 95% CI: 0.29–0.86; p = 0.013) and RDI-O (OR = 1.91; 95%CI: 1.06–3.39; p = 0.028). The early vs. late recurrence negatively correlated with OS regardless of the RDI-O (HR = 22.9 (95%CI: 13.9–37.6; p < 0.001).ConclusionsRDI-O < 60% in adjuvant therapy among stage III CC (especially in low-risk group) increases the risk of early recurrence within 18 months of surgery. Patients with early recurrence showed worse overall survival regardless of the RDI-O.

Treatment preferences in stage IA and IB testicular seminoma: multicenter study of Anatolian Society of Medical Oncology.

Approximately 75 % of patients with testicular seminoma present with stage I disease, and the probability of long-term survival approaches 100 %. However, the standard adjuvant treatment for stage I seminoma patients remains controversial, and there is no uniform consensus in the literature. The present study was performed to evaluate treatment preference and outcomes for men with stage I testicular seminoma. From 1997 to 2013, 282 patients with histologically confirmed stage IA and IB testicular seminoma who underwent orchiectomy were included. The outcomes of three management options and survivals were retrospectively analyzed. The prognostic significance of risk factors for relapse on survival was evaluated by univariate and multivariate analysis; in addition, the factors predicting relapse were also evaluated by logistic regression analysis. Of the 282 patients with stage I seminoma, 130 (46.1) received adjuvant radiotherapy (RT), 80 (28.4 %) were treated with adjuvant carboplatin, while the remaining 72 patients (25.5 %) underwent surveillance. At the time of analysis, the median follow-up period of 38.5 months; relapses were observed in 16 patients (22.3 %) on surveillance, in one patient (1.2 %) treated with adjuvant carboplatin and in ten patients (%7.7) who received adjuvant RT. The 5-year disease-free survival (DFS) rate for patients who underwent surveillance was worse than those of patients treated with adjuvant carboplatin and RT (64.2 vs. 97.7 vs. 91.9 %, respectively; p < 0.001). However, the 5-year overall survival (OS) rate for patients on surveillance was similar compared with the adjuvant treatment groups (100 vs. 92.3 vs. 97.4 %, respectively; p = 0.44). Univariate analysis showed that only the treatment approach (surveillance vs. adjuvant carboplatin vs. adjuvant RT) for DFS (p < 0.001), invasion of the rete testis (p = 0.041) and the presence of relapse (p < 0.001) for OS were important prognostic indicators. Multivariate analysis indicated that the treatment strategy for DFS (p < 0.001, HR 0.34) was an independent prognostic factor. Furthermore, a logistic regression analysis showed that adjuvant treatment was found to be an independent factor for predicting relapse (p = 0.004, odds ratio: 0.39). Our results indicate that adjuvant treatment with carboplatin or RT is associated with improved DFS compared with surveillance for men with stage I testicular seminoma after orchiectomy. Moreover, the treatment strategy is an important prognostic indicator for DFS and a predictive factor for relapse. Although adjuvant treatment, especially carboplatin, seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still feasible and the preferred management option after radical orchiectomy in men with stage I seminoma. More reliable predictive factors are needed to make treatment decisions.

The efficacy of oxaliplatin-based adjuvant chemotherapy for stage IV colorectal cancer after R0 resection.

638 Background: In previous phase III studies (MOSAIC and XELOXA trial), oxaliplatin based chemotherapy was shown to be a standard adjuvant treatment for stage III colorectal cancer (CRC). However, its efficacy for curatively resected stage IV CRC has not yet been clarified. In this retrospective study, we evaluate the efficacy of oxaliplatin based chemotherapy in adjuvant setting for curatively resected stage IV CRC. Methods: Eighty-three patients received adjuvant chemotherapy after R0 resection for Stage IV CRC in our institute between Mar 2007 and Feb 2013. Progression-free survival (PFS), overall survival (OS), completion rate of the treatment and safety were evaluated. Median follow-up time was 33.3 months. Results: Baseline characteristics were as follows (N=83): median age, 61; male/female, 46/37; ECOG PS0, all; colon/rectum, 54/29; synchronous/asynchronous, 41/42. Metastatic sites were liver in 46, lung in 11, peritoneum in 13, lymph node in 12 patients. Median PFS and OS were not reached. Three-year PFS and OS were 67.8% and 88.2%, respectively. Completion rate was 78.6% of the patients. In univariate analysis, completion of treatment, synchronous development and metastasis limited to lung were associated with better PFS, though not statistically significant. Confirmed regional lymph node metastasis of primary tumor showed a trend toward to concern with poor OS. Differences in metastatic site were not observed in both PFS and OS. Multivariate analysis revealed none as a significant prognostic factor. Conclusions: Compared the results to previous trial for stage III CRC, oxaliplatin based adjuvant chemotherapy for stage IV CRC after R0 resection was demonstrated to be consistent in tolerability and efficacy.

Retrospective analysis of 132 patients with stage I seminoma: Observation versus adjuvant radiation or chemotherapy in a single institution.

e15033 Background: Classically, radiotherapy (RT) has been the standard adjuvant treatment for stage I seminoma patients. Improvements in early relapse diagnosis have led high cure rates. Two cycles of adjuvant carboplatin present similar efficacy to radiotherapy with less toxicity have led to re-examination of the standard treatment approach. Methods: Retrospective study of 132 patients diagnosed with stage I seminoma from 1980-2010 who received whether treatment with RT, chemotherapy (Cht) or active surveillance (AS) after orchiectomy at one Universitary Hospital. The objective was to determine the relapse-free survival (RFS), overall survival (OS), and disease -specific survival (DSS). Results: Of the 132 patients, 68 were treated with prophylactic irradiation (paraaortic ± pelvic nodes, the median total dose radiation 26 Gy at 2 Gy per fraction), 33 with adjuvant chemotherapy (31 had carboplatin x 2, 2 had BEP x 2), and 31 underwent surveillance. Among the RT patients (median follow-up 121months), mean age was 40 years (range: 20-70) with mean tumor size of 5.5 cm (range: 1-14). 6% of them had rete testis involvement and 15% vascular invasion. There was 1 relapse with a median disease-free survival (DFS) of 103 months and no deaths from seminoma. RFS was 98% at 10 years. OS and DSS were 100% at 10years. Among the chemotherapy patients mean age was 30 years (range: 18-66) with mean tumor size of 6,18cm (range: 1,5-10). 9% of them had rete testis involvement and 60 % vascular invasion. With a median follow-up of 66 months, there was 1 relapse. Five-year RFS was 97%, OS and DSS were 100%. Among the observation patients (median follow-up 148 months), mean age was 35 years (range: 20-78) with mean tumor size of 3,7cm (range: 1,3-7). 6% of them had rete testis involvement and 6 % vascular invasion. There were 6 relapses with no deaths from seminoma. RFS was 80%, specific OS and DSS was 100% at 10 years. Of the patients who relapsed, all were rendered disease-free with chemotherapy; with non evidence disease at last follow-up. Conclusions: Consistent with published trials both radiotherapy, chemotherapy or active surveillance are safe and effective treatments with similar oncologic results.

Is There a Future for Bevacizumab in the Adjuvant Setting After the C-08 and AVANT Trials?

Fluoropyrimidine-based regimens have become the standard adjuvant treatment for stage III colorectal cancer (CRC). Despite the superior outcomes with adjuvant 5-FU/leucovorin/oxaliplatin schedules, nearly one third of node-positive CRC patients still recur. Bevacizumab is a recombinant humanized monoclonal antibody to vascular endothelial growth factor, which has demonstrated efficacy in terms of progression-free survival, and overall survival for patients with metastatic CRC. These positive results formed the basis to explore its role in the adjuvant setting. To answer the question of whether bevacizumab would add on overall and/or disease-free survival, two large randomized phase 3 trials (NSABP C-08 and AVANT) tested the addition of bevacizumab to standard oxaliplatin-based adjuvant chemotherapy in early-stage CRC patients. However, the addition of anti-angiogenic therapy to adjuvant scenario failed to improve disease-free survival and overall survival. This article aimed to explain the reasons why bevacizumab had no impact on the outcomes of adjuvant treatment of colorectal cancer.

Predicted Rates of Secondary Malignancies From Proton Versus Photon Radiation Therapy for Stage I Seminoma

Photon radiotherapy has been the standard adjuvant treatment for stage I seminoma. Single-dose carboplatin therapy and observation have emerged as alternative options due to concerns for acute toxicities and secondary malignancies from radiation. In this institutional review board-approved study, we compared photon and proton radiotherapy for stage I seminoma and the predicted rates of excess secondary malignancies for both treatment modalities. Computed tomography images from 10 consecutive patients with stage I seminoma were used to quantify dosimetric differences between photon and proton therapies. Structures reported to be at increased risk for secondary malignancies and in-field critical structures were contoured. Reported models of organ-specific radiation-induced cancer incidence rates based on organ equivalent dose were used to determine the excess absolute risk of secondary malignancies. Calculated values were compared with tumor registry reports of excess secondary malignancies among testicular cancer survivors. Photon and proton plans provided comparable target volume coverage. Proton plans delivered significantly lower mean doses to all examined normal tissues, except for the kidneys. The greatest absolute reduction in mean dose was observed for the stomach (119 cGy for proton plans vs. 768 cGy for photon plans; p < 0.0001). Significantly more excess secondary cancers per 10,000 patients/year were predicted for photon radiation than for proton radiation to the stomach (4.11; 95% confidence interval [CI], 3.22-5.01), large bowel (0.81; 95% CI, 0.39-1.01), and bladder (0.03; 95% CI, 0.01-0.58), while no difference was demonstrated for radiation to the pancreas (0.02; 95% CI, -0.01-0.06). For patients with stage I seminoma, proton radiation therapy reduced the predicted secondary cancer risk compared with photon therapy. We predict a reduction of one additional secondary cancer for every 50 patients with a life expectancy of 40 years from the time of radiation treatment with protons instead of photons. Proton radiation therapy also allowed significant sparing of most critical structures examined and warrants further study for patients with seminoma, to decrease radiation-induced toxicity.

Bronchiolite oblitérante avec pneumonie organisée après chimiothérapie de type FOLFOX 4

FOLFOX 4 chemotherapy (5-fluorouracil, leucovorin and oxaliplatin) is the standard adjuvant treatment for stage III colon cancer. The principal secondary effects described are haematological, gastro-intestinal or neurological. A single case of obliterative bronchiolitis with organising pneumonia has been described recently. We report the case of a female patient aged 74 years who, after 12 courses of FOLFOX 4 chemotherapy, developed acute onset of severe shortness of breath and a dry cough but remained afebrile. A thoracic CT-scan showed symmetrical bilateral interstitial infiltration that was reticular in appearance, and predominantly basal and peripheral in distribution. Broncho-alveolar lavage revealed an alveolitis with 9% eosinophils and 4% neutrophils. Transbronchial biopsies showed the appearances of obliterative bronchiolitis with organising pneumonia. Systemic corticosteroid treatment led to a remarkable clinical and functional improvement. To our knowledge, this is the second case of obliterative bronchiolitis with organising pneumonia that has been described following adjuvant treatment based on FOLFOX 4.

Primary colon cancer: ESMO Clinical Recommendations for diagnosis, adjuvant treatment and follow-up

Staging provides essential prognostic information relevant for choosing adequate therapy and should also identify patients with resectable distant metastases. Preoperative staging consists of clinical examination, blood counts, liver and renal function tests, carcino-embryonic antigen (CEA), chest X-ray or preferably chest CT-scan, CT scan of the abdomen including the pelvis and a colonoscopy of the entire large bowel, i.e. with postoperative repeat colonoscopy if proximal parts of the colon were not accessible preoperatively. Pathologic staging should be done according to the 2002TNM system with optional listing of the modified Dukes stage, as described in Table 1. Risk factors for colorectal cancer are: family history, familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) syndromes, hereditary non-polyposis colorectal cancer (HNPCC) syndrome, past history of colorectal cancer or adenoma, chronic ulcerative colitis and Crohn’s disease. prognosis

Cetuximab plus FOLFOX-4 for fully resected stage III colon carcinoma: scientific background and the ongoing PETACC-8 trial

The standard adjuvant treatment for stage III colon cancer in Europe is the 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX-4) regimen, given for 6 months. Cetuximab, a monoclonal antibody directed against the EGF receptor, appears to be effective and safe when combined with oxaliplatin-based regimens, including FOLFOX-4, in patients with metastatic colorectal cancer. PETACC-8, a randomized, multicenter, European Phase III trial, is comparing the efficacy of cetuximab plus FOLFOX-4 with that of FOLFOX-4 alone in patients with stage III colon cancer. The study began in December 2005 and approximately 2000 patients are to be enrolled in nine European countries. The primary end point is disease-free survival time, analyzed after a minimum follow-up of 3 years per patient. Secondary end points include overall survival, treatment compliance, safety and pharmacogenomic parameters.

Irinotecan Fluorouracil Plus Leucovorin Is Not Superior to Fluorouracil Plus Leucovorin Alone As Adjuvant Treatment for Stage III Colon Cancer: Results of CALGB 89803

Randomized studies have shown that irinotecan (CPT-11) extends survival in metastatic colorectal cancer patients when administered in second-line and when added to fluorouracil (FU) plus leucovorin (LV) in first-line therapy of metastatic colorectal cancer. When this study was initiated, FU plus LV was standard adjuvant treatment for stage III colon cancer. We evaluated the efficacy and safety of weekly bolus CPT-11 plus FU plus LV in the treatment of patients with completely resected stage III colon cancer. A total of 1,264 patients were randomly assigned to receive either standard weekly bolus FU plus LV regimen or weekly bolus CPT-11 plus FU plus LV. The primary end points of the study were overall survival (OS) and disease-free survival (DFS). Treatment arms were well-balanced for patient characteristics and prognostic variables. There were no differences in either DFS or OS between the two treatment arms. Toxicity, including lethal toxicity, was significantly higher on the CPT-11 plus FU plus LV arm. The addition of CPT-11 to weekly bolus FU plus LV did not result in improvement in DFS or OS in stage III disease, but did increase both lethal and nonlethal toxicity. This trial demonstrates that advances in the treatment of metastatic disease do not necessarily translate into advances in adjuvant treatment, and it reinforces the need for randomized controlled adjuvant studies.

Distress before chemotherapy predicts delayed but not acute nausea

Posttreatment nausea (PTN) is a common side effect of cytotoxic cancer chemotherapy. Previous retrospective research has suggested that the severity of PTN may be, in part, related to pretreatment psychological factors (e.g., emotional distress and expectations for nausea). The purpose of the present study was to examine these relationships prospectively, with distress and nausea expectations assessed by validated self-report measures completed in the clinic before the participants' first outpatient treatment infusion and with PTN (0-100) assessed by end-of-day diaries completed at home on each of the first 5 days after treatment. The participants were chemotherapy-naive women (N=56) scheduled for standard adjuvant treatment for stage I-II breast cancer (mean age=45.6 years). PTN was evaluated for acute (days 0-1) and delayed (days 2-5) responses. The results revealed a significant relationship between pretreatment distress and the severity of the patients' subsequent delayed nausea (p<0.007) but not a relationship with acute PTN (p<0.19). No significant relationships were seen between expectations and PTN. However, there was evidence of an additive effect of nausea expectations and distress, with the highest levels of delayed PTN seen in patients with both expectations and higher distress before treatment. The results suggest a selective effect of pre-infusion psychological variables on the delayed phase of nausea after chemotherapy, consistent with an emerging view that the different phases of nausea are mediated by different neural pathways. Future research should examine the possibility that delayed nausea, which the literature suggests is more resistant to antiemetic drugs than acute nausea, might be responsive to psychological interventions before initial treatments.

Effects of 5-fluorouracil adjuvant treatment of colon cancer

Since the late 1980s and early 1990s, 5-fluorouracil-based chemotherapy has been the standard adjuvant treatment for Stage III colon cancer. After the initial introduction of 5-fluorouracil in standard treatment protocols, several changes have been made based on results of randomized studies on various treatment regimens, including new cytotoxic agents. In Stage II patients, the role of adjuvant chemotherapy is debatable. However, there might be a role for adjuvant treatment in certain high-risk patients. Following a search of the Medline database, the results of randomized studies on 5-fluorouracil-based adjuvant therapy are reviewed, and future therapeutic options are discussed.

Reply: Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer

Reply: Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer

Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study

Intravenous fluorouracil and leucovorin is the standard adjuvant treatment for stage III colon cancer. However, oral adjuvant chemotherapy is attractive because it has low toxicity and greater convenience. We investigated the benefits of oral protein-bound polysaccharide K (PSK) with tegafur/uracil (UFT) as an adjuvant in stage II and III colorectal cancer. Patients were assigned to groups that received either 3 g PSK plus 300 mg UFT, or 300 mg UFT alone orally each day for a 2-year period following intravenous mitomycin C. Of 207 registered patients, 205 with stage II (n=123) or III (n=82) were analysed. The 5-year disease-free survival was 73.0% (95% CI 65.6–80.4%) with PSK (n=137) and 58.8% (95% CI 47.1–70.5%) in the controls (n=68) (P=0.016). Polysaccharide K reduced the recurrence by 43.6% (95% CI 4.5–66.7%) and mortality by 40.2% (95% CI −12.5 to 68.3%). The 5-year survival was 81.8% (95% CI 75.3–88.2%) in the PSK group and 72.1% (95% CI 61.4–82.7%) in the control group (P=0.056). In stage III patients, disease-free and overall survivals in patients receiving PSK were increased significantly: 60.0% (95% CI 47.1–72.9%) and 74.6% (95% CI 63.0–86.1%) in the PSK group as compared with 32.1% (95% CI 14.8–49.4%) and 46.4% (95% CI 28.0–64.9%) in the controls (P=0.002 and 0.003, respectively). Polysaccharide K prevented recurrence, particularly lung metastases (P=0.02; odds ratio 0.27; 95% CI 0.09–0.77). In the models, the presence of regional metastases (relative risk, 2.973; 95% CI 1.712–5.165; P<0.001), omission of PSK (relative risk, 2.106; 95% CI 1.221–3.633; P=0.007), and higher primary tumour (relative risk, 4.398; 95% CI 1.017–19.014; P=0.047) were each significant indicators of recurrence. Adverse effects were mild and compliance was good. Oral PSK with UFT reduced recurrence in stage II and III colorectal cancer, and increased survival in stage III.

National Cancer Institute Clinical Trials Program in Colorectal Cancer.

Colorectal cancer will be diagnosed in approximately 150,000 patients in the USA this year. Chemotherapy has recently been shown to improve survival when given as adjuvant therapy to surgery in patients with stage III colorectal cancer. Demonstration of this benefit required large, randomized controlled trials. Either 5-fluorouracil (5-FU) and leucovorin for 6 months or 5-FU and levamisole for 12 months are currently considered standard adjuvant treatment for stage III colorectal cancer. However, current adjuvant trials are comparing continuous infusion and intravenous bolus 5-FU regimens and oral uracil/Ftorafur with intravenous 5-FU and leucovorin, as well as studying the timing of chemotherapy in the adjuvant setting. Subsequent adjuvant trials will examine newer regimens with activity in advanced colorectal cancer, as well as the efficacy of monoclonal antibodies. Other trials will study which type of surgery is optimal and whether adjuvant therapy is helpful in stage II colon cancer. Trials in metastatic disease will focus on combinations of newer agents which may improve survival in this patient group. Studies in rectal cancer will focus on determining which agents are optimal in combination with radiation therapy in the adjuvant setting. Molecular characteristics of tumor cells are being defined, which may guide therapy in the future. Careful, logically designed clinical trials will hopefully provide more efficacious therapy for this common cancer.

Colorectal Cancer: Colorectal carcinoma: Current problems and future perspectives

Colorectal carcinoma represents a highly interesting model for the biological development of a solid tumor, the efficacy or primary and secondary prevention and the development of chemotherapeutic and immunologic strategies for adjuvant and/or neoadjuvant treatment is resectable stages. Adjuvant systemic 5-FU/levamisole is currently the standard adjuvant treatment for stage III colon cancer. 5-FU/folinic acid for 6 months seems to achieve equivalent results. Continuous infusion of 5-FU for 7 days postoperatively via the portal vein achieves also a comparable improvement in disease-free and overall survival. Beyond the long term systemic as well as short time intraportal chemotherapy, adjuvant immunotherapy with either 17-1A murine monoclonal antibody or autologous tumor vaccine achieves quite comparable results like adjuvant chemotherapy. Therefore the combination of these modalities might be of high interest for further investigation. The current EORTC study for colorectal cancer investigates the role of the combination of short time regional and long term systemic chemotherapy. For rectal cancer stage II and III adjuvant 5-FU plus radiation is currently the standard. However, further improvement seems possible with 5-FU given as continuous infusion during radiation; this approach is currently investigated in an ongoing Intergroup study. A further attractive approach, particularly for locally advanced, borderline resectable rectal cancer is the neoadjuvant combined modality treatment with 5-FU/folinic acid plus radiation followed by surgery and further adjuvant chemotherapy; this neoadjuvant treatment is currently being investigated in comparison to postoperative 5-FU/folinic acid plus radiation in an ongoing Intergroup study. Future protocols should also include immunotherapy with 17-1A antibody which significantly prolongs disease-free and overall survival also in rectal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)