International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer

BACKGROUND: The question of whether platinum-based adjuvant chemotherapy can improve outcomes in patients with early-stage epithelial ovarian cancer is an important one. We carried out a multicenter, open randomized trial to determine whether adjuvant chemotherapy would improve overall survival and prolong recurrence-free survival in women with early-stage epithelial ovarian cancer. METHODS: Between August 1991 and January 2000, 477 patients in 84 centers in five countries were randomly assigned to receive either adjuvant chemotherapy immediately following surgery (n = 241) or no adjuvant chemotherapy until clinically indicated (n = 236). Kaplan-Meier curves of overall survival and recurrence-free survival were compared using the Mantel-Cox version of the log-rank test. All statistical tests were two-sided. RESULTS: Women who received adjuvant chemotherapy had better overall survival than women who did not (hazard ratio [HR] of 0.66, 95% confidence interval [CI] = 0.45 to 0.97; P =.03). These results translate into 5-year survival figures of 70% for women who did not receive adjuvant chemotherapy and 79% for women who did receive adjuvant chemotherapy, a difference of 9% (95% CI = 1% to 15%). Adjuvant chemotherapy also improved recurrence-free survival (HR = 0.65; 95% CI = 0.46 to 0.91; P =.01). These results translate into 5-year recurrence-free survival figures of 62% for women who did not receive adjuvant chemotherapy and 73% for women who did receive adjuvant chemotherapy, a difference of 11% (95% CI = 3% to 18%). CONCLUSION: These results suggest that platinum-based adjuvant chemotherapy improves survival and delays recurrence in patients with early-stage ovarian cancer.     

Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma: European Organisation for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm trial

BACKGROUND: All randomized trials of adjuvant chemotherapy for early-stage ovarian cancer have lacked the statistical power to show a difference in the effect on survival between adjuvant chemotherapy and no adjuvant chemotherapy. They have also not taken into account the adequacy of surgical staging. We performed a prospective unblinded, randomized phase III trial to test the efficacy of adjuvant chemotherapy in patients with early-stage ovarian cancer, with emphasis on the extent of surgical staging. METHODS: Between November 1990 and January 2000, 448 patients from 40 centers in nine European countries were randomly assigned to either adjuvant platinum-based chemotherapy (n = 224) or observation (n = 224) following surgery. Endpoints were overall survival and recurrence-free survival, and the analysis was on an intention-to-treat basis. The Kaplan-Meier method was used to perform time-to-event analysis, and the log-rank test was used to compare differences between treatment arms. Statistical tests were two-sided. RESULTS: After a median follow-up of 5.5 years, the difference in overall survival between the two trial arms was not statistically significant (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.44 to 1.08; P =.10). Recurrence-free survival, however, was statistically significantly improved in the adjuvant chemotherapy arm (HR = 0.63, 95% CI = 0.43 to 0.92; P =.02). Approximately one-third of patients (n = 151) had been optimally staged and two-thirds (n = 297) had not. Among patients in the observation arm, optimal staging was associated with a statistically significant improvement in overall and recurrence-free survival (HR = 2.31 [95% CI = 1.08 to 4.96]; P =.03 and HR = 1.82 [95% CI = 1.02 to 3.24] P =.04, respectively). No such association was observed in the chemotherapy arm. In the non-optimally staged patients, adjuvant chemotherapy was associated with statistically significant improvements in overall and recurrence-free survival (HR = 1.75 [95% CI = 1.04 to 2.95]; P =.03 and HR = 1.78 [95% CI = 1.15 to 2.77]; P =.009, respectively). In the optimally staged patients, no benefit of adjuvant chemotherapy was seen. CONCLUSION: Adjuvant chemotherapy was associated with statistically significantly improved recurrence-free survival in patients with early-stage ovarian cancer. The benefit of adjuvant chemotherapy appeared to be limited to patients with non-optimal staging, i.e., patients with more risk of unappreciated residual disease.     

Optimal treatment of early-stage ovarian cancer

BackgroundThere is no clear consensus regarding systemic treatment of early-stage ovarian cancer (OC). Clinical trials are challenging because of the relatively low incidence and good prognosis. Initial results of the International Collaborative Ovarian Neoplasm (ICON)1 trial demonstrated benefit in both overall survival (OS) and recurrence-free survival (RFS) with adjuvant chemotherapy. We report results of 10-year follow-up to establish whether benefits are maintained longer term and discuss how this and other available evidence from randomised trials can be used to guide treatment options regarding the need for, and choice of, adjuvant chemotherapy regimen.Patients and methodsICON1 recruited women with OC following primary surgery in whom there was uncertainty as to whether adjuvant chemotherapy was indicated. Patients were randomly assigned to adjuvant or no adjuvant chemotherapy. Platinum-based chemotherapy was recommended and 87% received single-agent carboplatin. Analyses of long-term treatment benefits and interaction with risk groups were carried out. A high-risk group of women was defined with stage 1B/1C grade 2/3, any stage 1 grade 3 or clear-cell histology.ResultsWith a median follow-up of 10 years, the estimated hazard ratio (HR) for RFS was 0.69 [95% confidence interval (CI) 0.51–0.94, P = 0.02] and OS 0.71 (95% CI 0.52–0.98, P = 0.04) in favour of chemotherapy. In absolute terms, there was a 10% (60%–70%) improvement in RFS and a 9% (64%–73%) improvement in OS; the benefit of chemotherapy might be greater in high-risk disease (18% improvement in OS). Uncertainty remains about the optimal chemotherapy regimen. The only randomised trial data available are from a subset of 120 stage 1 patients in ICON3 where the treatment difference, comparing carboplatin with carboplatin/paclitaxel was estimated with relatively wide CIs [progression-free survival HR = 0.71 (95% CI 0.39–1.32) and OS HR = 0.98 (95% CI 0.49–1.93)].ConclusionsExtended follow-up from ICON1 confirms that adjuvant chemotherapy should be offered to women with early-stage OC, particularly those with high-risk disease.Clinical trial numbersISRCTN11916376 for ICON1 and ISRCTN57157825 for ICON3.     

Can patients with relapsed, previously untreated, stage I epithelial ovarian cancer be successfully treated with salvage therapy?

PURPOSE: The role of adjuvant chemotherapy in early-stage epithelial ovarian cancer (EOC) has been controversial. We have previously reported the cases of patients managed with a policy of observation only. We now present the salvage rate for the patients in that study who experienced relapse. PATIENTS AND METHODS: One hundred ninety-four patients with stage I EOC presenting between 1980 and 1994 received no adjuvant chemotherapy, but were treated with platinum-based chemotherapy at relapse. We calculated the progression-free survival (PFS) and overall survival (OS) for the whole cohort and the salvage rate for those who experienced relapse. We defined salvage as freedom from relapse for 5 years after platinum treatment. RESULTS: Sixty-one (31%) of 194 patients experienced relapse, and 55 received platinum-based chemotherapy. Twenty-four percent were progression-free at 5 years after this treatment. Clear-cell histology and cyst rupture before the patients' original surgery were independent prognostic factors for PFS after salvage chemotherapy. The OS for all 194 patients is 72% at 10 years (median follow-up, 8.7 years), with an 80% disease-specific survival (DSS). CONCLUSION: We have shown that some patients with stage I EOC can be successfully treated with a salvage chemotherapy regimen after a policy of observation only. Interestingly, approximately 30% of stage I patients who die within 10 years do so from causes other than EOC (OS, 72%; DSS, 80%). Our findings need to be taken into consideration when the results from recent randomized trials of adjuvant chemotherapy in this patient population (International Collaborative Ovarian Neoplasm Trial 1/European Organization for Research and Treatment of Cancer Adjuvant Chemotherapy in Ovarian Neoplasm Trial) are being discussed with patients.     

Systematic review of adjuvant care for women with Stage I ovarian carcinoma

BACKGROUND: Several adjuvant care interventions to treat women with Stage I ovarian carcinoma have been studied. The aim of the current systematic review was to determine the optimal strategy for adjuvant care for women with Stage I ovarian carcinoma. METHODS: A systematic search was conducted to find randomized controlled trials published between 1965 and April 2004 that examined adjuvant therapy (e.g., chemotherapy and radiotherapy) for women with Stage I ovarian carcinoma. RESULTS: Thirteen randomized controlled trials were identified that compared adjuvant therapies for women with Stage I ovarian carcinoma. Eight of these trials reported results only for patients with Stage I disease. The majority of patients in the five randomized trials that compared adjuvant chemotherapy with no chemotherapy did not receive lymphadenectomy as part of their surgical staging. The pooled results for Stage I patients indicated a survival benefit (relative risk [RR], 0.74; 95% confidence interval [CI], 0.58-0.94; P = 0.01), and a benefit in terms of a reduced risk of developing disease recurrence (RR, 0.70; 95% CI, 0.58-0.86; P = 0.0004) favoring adjuvant chemotherapy. Platinum-based adjuvant chemotherapy was reported to improve overall 5-year survival (absolute survival difference 8%; 95% CI, 2-12%; hazard ratio, 0.67; 95% CI, 0.50-0.90; P = 0.008). CONCLUSIONS: Adjuvant platinum-based chemotherapy for women with Stage I ovarian carcinoma improved survival and reduced the risk of recurrent disease. The optimally staged group accounted for approximately 10% of women with Stage I disease. The role of adjuvant chemotherapy in optimally staged patients (especially those with good prognostic factors) has not been assessed adequately.     

Treatment of patients with early epithelial ovarian cancer

PURPOSE OF REVIEW: During 2003, the first randomized trials were published comparing adjuvant platin-based chemotherapy versus no treatment in early epithelial ovarian cancer. RECENT FINDINGS: Recent findings of the European Organisation for Research and Treatment of Cancer Adjuvant ChemoTherapy In Ovarian Neoplasm and International Collaborative Ovarian Neoplasm-1 trials showed an improvement of overall survival of 8% in patients treated with adjuvant platin-based chemotherapy compared with observation. In a subgroup analysis, in 150 optimally surgically staged patients of the European Organisation for Research and Treatment of Cancer Adjuvant ChemoTherapy In Ovarian Neoplasm trial, there appears to be no benefit of adjuvant chemotherapy. In past years, it has been shown that degree of differentiation is a much stronger predictor of recurrence in early ovarian cancer than International Federation of Gynaecology and Obstetrics subclassification (Ia, Ib, Ic). It has also been shown that patients with bilateral tumors (Ib) have the same prognosis as International Federation of Gynaecology and Obstetrics stage Ic patients. SUMMARY: During the past year, it has been shown that platin-based adjuvant chemotherapy improves recurrence-free and overall survival in early epithelial ovarian cancer. It should be emphasized, however, that this was demonstrated in patients in whom the true nature of early stage disease was doubtful in many patients due to incomplete surgical staging. In a subgroup of patients who are optimally surgically staged, adjuvant chemotherapy may be less effective. Theoretically, only a future trial randomizing optimal surgical staging versus adjuvant chemotherapy may be able to provide definitive conclusions, but such a trial would be almost impossible to conduct. In the meantime, optimal staging is advocated in all patients who are fit enough to undergo this procedure. Degree of differentiation should be incorporated in a new International Federation of Gynaecology and Obstetrics classification for stage I disease and in clinical decision making.     

Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

PURPOSE: The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. PATIENTS AND METHODS: Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. RESULTS: Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients <40 years of age and with estrogen receptor-positive tumors, ovarian suppression significantly decreased the risk of recurrence (P = 0.01). CONCLUSIONS: The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.     

Effect of cognitive-existential group therapy on survival in early-stage breast cancer.

PURPOSE: Cognitive-existential group therapy (CEGT) was developed to improve mood and mental attitude toward cancer in women with early-stage breast cancer receiving adjuvant chemotherapy. Given the debate about group therapy's association with increased survival in women with metastatic breast cancer, we were curious to check its effect at a much earlier stage in the cancer journey. PATIENTS AND METHODS: We randomly assigned 303 women with early-stage breast cancer who were receiving adjuvant chemotherapy to either 20 sessions of weekly group therapy plus three relaxation classes (n = 154) or to a control condition of three relaxation classes alone (n = 149). The primary outcome was survival. RESULTS: CEGT did not extend survival; the median survival time was 81.9 months (95% CI, 64.8 to 99.0 months) in the group-therapy women and 85.5 months (95% CI, 67.5 to 103.6 months) in the control arm. The hazard ratio for death was 1.35 (95% CI, 0.76 to 2.39; P = .31). In contrast, histology and axillary lymph node status were significant predictors of survival. Low-grade histology yielded a hazard ratio of 0.342 (95% CI, 0.17 to 0.69), and axillary lymph node-negative status yielded a hazard ratio of 0.397 (95% CI, 0.20 to 0.78). CONCLUSION: CEGT does not prolong survival in women with early-stage breast cancer.     

Is There a Survival Benefit of Adjuvant Chemotherapy in Stage IC1 Epithelial Ovarian Cancer Patients? A Meta-Analysis

The purpose of the present systematic review is to clarify whether adjuvant chemotherapy improves survival rates in women with stage IC1 ovarian cancer. We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar. We considered comparative observational studies and randomized trials that investigated survival outcomes (progression-free (PFS) and overall survival (OS)) among women with intraoperative rupture of early-stage epithelial ovarian cancer who received adjuvant chemotherapy and those that did not. Eleven studies, which recruited 7556 patients, were included. The risk of bias was defined as moderate after assessment with the Risk of Bias in non-Randomized Trials tool. Meta-analysis was performed with RStudio. Seven studies investigated the impact of adjuvant chemotherapy on recurrence-free survival of patients experiencing intraoperative cyst rupture for otherwise stage I ovarian cancer. The outcome was not affected by the use of adjuvant chemotherapy as the effect estimate was not significant (HR 1.24, 95% CI 0.74, 2.04). The analysis of data from 5 studies similarly revealed that overall survival rates were comparable among the two groups (HR 0.75, 95% CI 0.54, 1.05). This meta-analysis did not detect any benefit from adjuvant chemotherapy for stage IC ovarian cancer patients with cyst rupture. However, conclusions from this investigation are limited by a study population which included multiple histologic subtypes, high and low grade tumors and incompletely staged patients.     

Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial

BACKGROUND: Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer (NSCLC) is not known. We aimed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC. METHODS: 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were randomly assigned to observation (n=433) or to 30 mg/m(2) vinorelbine plus 100 mg/m(2) cisplatin (n=407). Postoperative radiotherapy was not mandatory and was undertaken according to every centre's policy. The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN95053737. FINDINGS: 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment. 301 (36%) patients had stage IB disease, 203 (24%) had stage II disease, and 325 (39%) had stage IIIA disease. Tolerance to chemotherapy mainly included neutropenia in 335 (92%) patients and febrile neutropenia in 34 (9%); seven (2%) toxic deaths were also recorded. Compliance was greater with cisplatin than with vinorelbine (median dose intensity 89% [range 17-108] vs 59% [17-100]). After a median follow-up of 76 months (range 43-116), median survival was 65.7 months (95% CI 47.9-88.5) in the chemotherapy group and 43.7 (35.7-52.3) months in the observation group. Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls (hazard ratio 0.80 [95% CI 0.66-0.96]; p=0.017). Overall survival at 5 years with chemotherapy improved by 8.6%, which was maintained at 7 years (8.4%). INTERPRETATION: Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC, better defining indication of adjuvant chemotherapy.     

Treatment Outcomes of Gemcitabine in Refractory or Recurrent pithelial Ovarian Cancer Patients

Background: To study the response rate (RR), progression-free survival (PFS) and toxicity profiles of recurrent pithelial ovarian cancer (EOC) patients treated with gemcitabine. Materials and Methods: Recurrent EOC patients who were treated with gemcitabine between January 2000 and December 2013 at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital were identified and medical records were reviewed. Clinico-pathological features including data of gemcitabine treatment, response and toxicity were collected. Results: We identified 43 EOC patients who had gemcitabine treatment. All except one patient who did not receive any adjuvant treatment, had received platinum-based chemotherapy. Among these 42 patients, 31.0% had refractory cancer to first-line chemotherapy while 69.0% had recurrence with 48.8% being platinumsensitive. The total cycles of gemcitabine used were 203 (median 4, range 2-9 cycles). Overall RR was 11.6%: 19% in platinum-sensitive vs 4.5% in platinum-resistant groups (p=0.158) and 42.9% in the patients having gemcitabine together with platinum vs 5.6% using gemcitabine alone (P=0.024). Median PFS was 3.6 months (95% confidence interval [CI], 2.73-4.49 months): 8.1 months (95% CI, 2.73-4.49 months) in combination regimen vs 3.2 months (95% CI, 2.01-4.42 months) in single regimen (p=0.077) and 8.1 months (95% CI, 4.73-11.48 months) with the gemcitabine combination vs 2.7 months (95% CI, 1.98-3.38 months) by single gemcitabine in platinum sensitive patients (P=0.007). Common toxicities were hematologic which were well tolerated and manageable. Conclusions: Gemcitabine has modest activity in pre-treated EOC. A combination regimen had higher activity than single agent in platinum sensitive patients with a significant improvement in RR and PFS.     

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: A prospective randomized controlled multi-center trial

Background and purpose: Triple-negative breast cancer (TNBC) presents a high risk breast cancer that lacks the benefit from hormone treatment, chemotherapy is the main strategy even though it exists in poor prognosis. Use of adjuvant radiation therapy, which significantly decreases breast cancer mortality, has not been well described among poor TNBC women. The aim of this study was to evaluate whether the combination of chemotherapy and radiotherapy could significantly increase survival outcomes in TNBC women after mastectomy. Patients and methods: A prospective randomized controlled multi-center study was performed between February 2001 and February 2006 and comprised 681 women with triple-negative stage I–II breast cancer received mastectomy, of them, 315 cases received systemic chemotherapy alone, 366 patients received radiation after the course of chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were estimated. Simultaneously local and systemic toxicity were observed. Results: After a median follow-up of 86.5 months, five-year RFS rates were 88.3% and 74.6% for adjuvant chemotherapy plus radiation and adjuvant chemotherapy alone, respectively, with significant difference between the two groups (HR 0.77 [95% CI 0.72, 0.98]; P = 0.02). Five-year OS significantly improved in adjuvant chemotherapy plus radiation group compared with chemotherapy alone (90.4% and 78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P = 0.03). No severe toxicity was reported. Conclusions: Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.     

Adjuvant treatment for early epithelial ovarian cancer: Results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P)

BACKGROUND: From 1983 to 1990, 271 consecutive patients with stage I ovariancancer entered two randomised trials, aimed at assessing therole of adjuvant chemotherapy after radical surgery in earlystages of ovarian cancer.Trial I compared cisplatin (50 mg/m²with repeated courses every 28 days for 6 cycles) to no furthertherapy in F.I.G.O.stage la & b Grade U-IH patients; trialII compared cisplatin (same dose and schedule) to ³²P in Ian& bii and Ic patients METHODS: Both studies were multicentric and centrally randomized. Treatmentwas allocated by phone and stratified by center. All patientssatisfying major eligibility criteria (histological diagnosisof ovarian carcinoma, correct F.I.G.O. stage and grade, no previousneoplasms) were analysed according to treatment allocated byrandomisation. RESULTS: With a median observation time of 16 months, cisplatin significantlyreduced the relapse rate by 65% (HR = 0.35; 95% CI = 0.14–0.89,p = 0.028; Cox Model) in trial I and 61% (HR = 0.39; 95% CI= 0.19–0.77, p = 0.007; Cox Model) in trial II. Survivalwas not significantly different (trial I – Kaplan-Meieroverall 5-year survival: cisplatin = 88%, control = 82%, HR= 1.15; 95% CI = 0.44 – 2.98; p = 0.773; Cox Model); trialII – overall 5-year survival: cisplatin = 81%, 32P = 79%,HR = 0.72; 95% CI = 0.37–1.43; p = 0.354; Cox model).In both studies the risk of dying after relapse increased forpatients originally randomized to the cisplatin arms: in trialI, 6 of 7 patients in the cisplatin relapsed arm and died oftumor compared with 8 of 14 patients in the control arm. Intrial II, 11 of 12 patients on cisplatin, and 18 of 26 on 32Psuccumbed to tumor recurrence. CONCLUSION: Adjuvant cisplatin treatment in early ovarian cancer significantlyprevents relapse in comparison to ³²P in Stage IC patients orto no immediate treatment in earlier Stage women. The impactof cisplatin adjuvant treatment on survival remains, however,unclear. early ovarian neoplasm, randomised trial, chemotherapy     

Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study).

BACKGROUND: This randomized, multicenter, phase III trial evaluated the efficacy and safety of the combination of epirubicin, leucovorin, 5-fluorouracil and etoposide (ELFE regimen) as adjuvant therapy for radically resected gastric cancer patients. PATIENTS AND METHODS: From June 1996 to June 2001, 228 stage IB-IIIB gastric cancer patients were enrolled. All patients received a total or subtotal gastrectomy with at least a D1 lymphoadenectomy and were randomly assigned to receive surgery alone or surgery followed by chemotherapy. RESULTS: A total number of 630 cycles was delivered with a median number of 5. With a median follow-up of 60 months, the 5-year overall survival (OS) was 48% in the treatment arm and 43.5% in the control arm [hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.69-1.21; P = 0.610); the 5-year disease-free survival (DFS) was 44% in the treatment arm and 39% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.305). In node-positive patients, the 5-year OS was 41% in the treatment arm and 34% in the control arm (HR 0.84; 95% CI 0.69-1.01; P = 0.068), while the 5-year DFS was 39% in the treatment arm and 31% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.051). The most common grade 3-4 toxic effects according to World Health Organization criteria were hematological and gastrointestinal. CONCLUSIONS: In radically resected gastric cancer patients, adjuvant chemotherapy with ELFE regimen does not improve OS over surgery alone.     

Epidermal Growth Factor Receptor Mutation Status and Adjuvant Chemotherapy in Resected Advanced Non–Small-Cell Lung Cancer

IntroductionThis study was to assess the association of epidermal growth factor receptor (EGFR) mutation status and efficacy of adjuvant chemotherapy in patients with fully resected IIIA-N2 non–small-cell lung cancer (NSCLC).Materials and MethodsTumor samples (n = 150) from patients with IIIA-N2 NSCLC who either had or had not received paclitaxel plus carboplatin or vinorelbine plus carboplatin doublet adjuvant chemotherapy were analyzed for EGFR mutations. The association of the presence of EGFR mutations and survival was assessed.ResultsMutations were identified in 43 (28.7%) patients (n = 25 in the no chemotherapy [observation] arm and n = 18 in the chemotherapy arm). Patients with EGFR mutations had statistically significant improved disease-free survival (41 months [95% CI, 25.1-56.9 months] vs. 20 months [95% CI, 15.0-25.0 months]; 2P = .005) and overall survival (50 months [95% CI, 37.6-62.4 months] vs. 25 months [95% CI, 20.8-29.2 months]; 2P = .001), regardless of treatment. The patients with wild-type EGFR had greater overall survival with chemotherapy compared with no adjuvant therapy (hazard ratio [HR] 4.748 [95% CI, 2.844-7.928]; 2P < .001). In contrast, in patients with EGFR mutation in the observation group compared with the chemotherapy group had longer median disease-free survival (49 months [95% CI, 35.1-62.9 months] for the observation arm vs. 30 months [95% CI, 23.8-36.2 months] for the chemotherapy arm, 2P = .195) and overall survival (59 months [95% CI, 43.9-74.1 months] vs. 33 months [95% CI, 24.7-41.3 months]; 2P = .050).ConclusionsIn this exploratory study, the status of EGFR mutations was associated with different clinical outcomes in patients with resected IIIA-N2 NSCLC. Further studies are required to confirm that a patient's adjuvant treatment may be customized to their EGFR mutational status.     

Adjuvant chemotherapy for elderly patients with stage I non-small-cell lung cancer ≥4 cm in size: an SEER–Medicare analysis

We have used population-based data from the SEER–Medicare registry to show that adjuvant chemotherapy is associated with improved survival among elderly patients with early-stage non-small-cell lung cancer ≥4 cm. These findings extend the results of a prior RCT to the growing population of older patients with cancer.BackgroundThe role of adjuvant chemotherapy for non-small-cell lung cancer (NSCLC) stage I patients with tumors size ≥4 cm is not well established in the elderly.Patients and methodsWe identified 3289 patients with stage I NSCLC (T2N0M0 and tumor size ≥4 cm) who underwent lobectomy from the Surveillance, Epidemiology and End Results (SEER)–Medicare linked database diagnosed from 1992 to 2009. Overall survival and rates of serious adverse events (defined as those requiring admission to hospital) were compared between patients treated with resection alone, platinum-based adjuvant chemotherapy, or postoperative radiation (PORT) with or without adjuvant chemotherapy. Propensity scores for receiving each treatment were calculated and survival analyses were conducted using inverse probability weights based on the propensity score.ResultsOverall, 84% patients were treated with resection alone, 9% received platinum-based adjuvant chemotherapy, and 7% underwent PORT with or without adjuvant chemotherapy. Adjusted analysis showed that adjuvant chemotherapy [hazard ratio (HR), 0.82; 95% confidence interval (CI) 0.68–0.98] was associated with improved survival compared with resection alone. Conversely, the use of PORT with or without adjuvant chemotherapy (HR 1.91; 95% CI 1.64–2.23) was associated with worse outcomes. Patients receiving adjuvant chemotherapy had more serious adverse events compared with those treated with resection alone, with neutropenia (odds ratio, 21.2; 95% CI 5.8–76.6) being most significant. No significant difference was observed in rates of fever, cytopenias, nausea, and renal dysfunction.ConclusionsPlatinum-based adjuvant chemotherapy is associated with reduced mortality and increased serious adverse events in elderly patients with stage I NSCLC and tumor size ≥4 cm.     

The impact of lymph node dissection and adjuvant chemotherapy on survival: A nationwide cohort study of patients with clinical early-stage ovarian cancer

IntroductionTo establish the impact of lymph node dissection and chemotherapy on survival in patients with early-stage epithelial ovarian cancer (EOC).MethodsAll Dutch patients with International Federation of Gynaecology and Obstetrics (FIGO) stage I–IIA and IIIA1 EOC between 2000 and 2012 were included. Data concerning age, stage, tumour grade, histological subtype, hospital type, lymph node dissection, adjuvant chemotherapy and survival were extracted from the Netherlands Cancer Registry.ResultsOf 3658 patients included, 1813 (49.6%) had lymph nodes removed. Relative survival of patients with lymph node dissection (including those with lymph node metastases) was significantly better than that of patients without, also after correcting for stage, tumour grade, histology and age (89% and 82%, respectively; relative excess risk [RER], 0.64; 95% confidence interval [CI]: 0.52–0.78). There was a positive correlation between the number of removed lymph nodes and overall survival (after excluding patients with lymph node metastases). Of patients with stage I–IIA EOC who had ≥10 lymph nodes removed, there was no difference in relative survival between those who received chemotherapy and those who did not (RER, 0.51; 95% CI: 0.15–1.64). This was also true for a subgroup of patients with high-risk features (stage IC and IIA and/or tumour grade 3 and/or clear cell histology [RER, 0.90; 95% CI: 0.46–1.99]).ConclusionAdequate dissection of at least 10 but preferably ≥20 lymph nodes should be standard procedure for the staging of early-stage EOC. Adjuvant chemotherapy after an adequate lymph node dissection does not seem to contribute to a better relative survival.     

Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial

The results of the PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy regarding overall survival, disease-free survival, and recurrence rates after preoperative (chemo)radiotherapy and TME surgery in yp stage II and III rectal cancer patients.BackgroundThe discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME).Patients and methodsThe PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8–2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival.ResultsOf 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62–1.39;P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60–1.07;P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39).ConclusionThe PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual.Registration numberDutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.     

No socioeconomic inequalities in ovarian cancer survival within two randomised clinical trials

Background:

Ovarian cancer is the leading cause of death among cancers of the female genital tract, with poor outcomes despite chemotherapy. There was a persistent socioeconomic gradient in 1-year survival in England and Wales for more than 3 decades (1971–2001). Inequalities in 5-year survival persisted for more than 20 years but have been smaller for women diagnosed around 2000. We explored one possible explanation.

Methods:

We analysed data on 1406 women diagnosed with ovarian cancer during 1991–1998 and recruited to one of two randomised clinical trials. In the second International Collaborative Ovarian Neoplasm (ICON2) trial, women diagnosed between 1991 and 1996 were randomised to receive either the three-drug combination cyclophosphamide, doxorubicin and cisplatin (CAP) or single-agent carboplatin given at optimal dose. In the ICON3 trial, women diagnosed during 1995–1998 were randomised to receive either the same treatments as ICON2, or paclitaxel plus carboplatin.Relative survival at 1, 5 and 10 years was estimated for women in five categories of socioeconomic deprivation. The excess hazard of death over and above background mortality was estimated by fitting multivariable regression models with Poisson error structure and a dedicated link function in a generalised linear model framework, adjusting for the duration of follow-up and the confounding effects of age, Federation of Gynecology and Obstetrics (FIGO) stage and calendar period.

Results:

Unlike women with ovarian cancer in the general population, no statistically significant socioeconomic gradient was seen for women with ovarian cancer treated in the two randomised controlled trials. The deprivation gap in 1-year relative survival in the general population was statistically significant at −6.7% (95% CI (−8.1, −5.3)), compared with −3.6% (95% CI (−10.4, +3.2)) in the trial population.

Conclusions:

Although ovarian cancer survival is significantly lower among poor women than rich women in England and Wales, there was no evidence of an association between socioeconomic deprivation and survival among women with ovarian cancer who were treated and followed up consistently in two well-conducted randomised controlled trials. We conclude that the persistent socioeconomic gradient in survival among women with ovarian cancer, at least for 1-year survival, may be due to differences in access to treatment and standards of care.     

Randomized controlled trial of single-agent paclitaxel versus cyclophosphamide, doxorubicin, and cisplatin in patients with recurrent ovarian cancer who responded to first-line platinum-based regimens.

PURPOSE: To assess the activity, efficacy, and tolerability of single-agent paclitaxel and a platinum-containing regimen in previously treated patients with recurrent ovarian cancer. PATIENTS AND METHODS: Patients who achieved complete remission with platinum-based regimens and whose disease recurred after a progression-free interval of more than 12 months were included in the study. Every 21 days, patients received paclitaxel 175 mg/m(2) intravenously (IV) over 3 hours or cyclophosphamide 500 mg/m(2), doxorubicin 50 mg/m(2), and cisplatin 50 mg/m(2) (CAP) IV. RESULTS: Between June 1992 and May 1995, 97 consecutive patients with assessable or measurable disease were randomized to paclitaxel (n = 50) or CAP (n = 47). The median number of cycles on each arm was six. Toxicities included grade 3/4 leukopenia (4% for paclitaxel v 34% for CAP), grade 3/4 neutropenia (13% v 36%), grade 1/2 myalgia (19% v 4%), allergic reactions (15% v 2%), and grade 2/3 nausea and vomiting (17% v 51%). Complete responses were achieved in 17% and 30% of patients receiving paclitaxel and CAP, respectively, and partial responses were achieved in 28% and 25%, respectively (P =.062). At a median follow-up time of 49 months, median progression-free intervals were 9 months for paclitaxel and 15.7 months for CAP (Cox analysis: hazards ratio [HR], 0.60; 95% confidence interval [CI], 0.37 to 0.97; P =.038); median overall survival times were 25.8 months for paclitaxel and 34.7 months for CAP (Cox analysis: HR, 0.58; 95% CI, 0.34 to 0.98; P =.043). CONCLUSION: Rechallenge with either single-agent paclitaxel or platinum-based chemotherapy is effective in this patient population. Preliminary results suggest that single-agent paclitaxel may not be as active as platinum-based chemotherapy in recurrent ovarian cancer. Larger randomized trials are needed.