Mucinous advanced epithelial ovarian carcinoma: clinical presentation and sensitivity to platinum–paclitaxel-based chemotherapy,the GINECO experience

BackgroundAdvanced mucinous epithelial ovarian carcinoma (mEOC) has been associated with a worse prognosis than the more common serous epithelial ovarian carcinomas (sEOC), but it remains unclear whether this observation reflects a more aggressive clinical presentation and/or chemoresistance.Patients and methodsData from four randomized phase III and one phase II advanced epithelial ovarian carcinoma (EOC) first-line clinical trials were retrospectively collected, yielding 1118 patients with advanced EOC (International Federation of Gynecology and Obstetrics stages IIB–IV), 85% of whom were treated with paclitaxel (Taxol)-carboplatin-based chemotherapy.ResultsBased on 786 patients with sEOC and 54 (5%) with mEOC, peritoneal carcinomatosis were more limited in mEOC, which was more frequently stages IIB–IIIB (32% versus 19%, P = 0.001) and had more frequently macroscopic complete resection after initial surgery (50% of stages II–III versus 30%, P = 0.02). In contrast, visceral metastases (stage IV) were more frequent in mEOC (30% versus 15%, P = 0.004). mEOC had a lower response rate to carboplatin–paclitaxel, and shorter progression-free and overall survival rates, for both stage IV and optimally debulked stages II–III patients.ConclusionsAdvanced mEOC appears to be highly chemoresistant and complete resection of peritoneal metastases is unable to reverse its poor prognosis. New therapeutic options are needed.     

Mucinous histology predicts for reduced fluorouracil responsiveness and survival in advanced colorectal cancer.

BACKGROUND: Mucinous carcinoma of the colon and rectum (mucinous CRC) is a histological subtype of colorectal adenocarcinoma for which there is little data on chemotherapy responsiveness. The purpose of this study was to investigate specifically the efficacy of fluorouracil-based first-line chemotherapy in patients with advanced mucinous CRC. PATIENTS AND METHODS: All patients with advanced mucinous CRC enrolled in three prospective randomized trials evaluating infused 5-fluorouracil as first-line treatment were compared with patients with non-mucinous subtypes enrolled in the same trials in a case-control study. Prognostic factors associated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. RESULTS: The study included 135 patients (45 cases and 90 controls). The response rates for cases and controls were 22% [95% confidence interval (CI), 11% to 38%] and 47% (95% CI, 36.1% to 58.2%), respectively (P=0.0058). Median OS for the mucinous CRC patients was 11.8 months (95% CI, 8.87-14.8) compared with 17.9 months (95% CI, 13.38-22.39) in the control group (univariate analysis, P=0.056); after correcting for significant prognostic factors by multivariate Cox regression analysis, P=0.0372 and hazard ratio (HR)=1.497 (1.02-2.19). CONCLUSION: Patients with advanced mucinous CRC have a poorer response to fluorouracil-based first-line chemotherapy and reduced survival compared with patients with non-mucinous CRC.     

Palliative chemotherapy for non-transitional cell carcinomas of the urothelial tract

Non-transitional cell carcinomas of the urothelial tract comprise 5–10% of urothelial cancers. Clinical information regarding the clinical behavior and chemotherapy outcome of non-transitional cell carcinomas of the urothelial tract are incomplete due to their rarity. The object of this study was to evaluate the clinical features and the efficacy of palliative chemotherapy in advanced non-transitional cell carcinomas of the urothelial tract. We analyzed the clinical records of 21 consecutive patients who received palliative chemotherapy for unresectable or metastatic non-transitional cell carcinomas of the urothelial tract between January 1995 and November 2007. All the 21 patients received first-line chemotherapy with platinum-based regimens which are known to be effective in transitional cell urothelial carcinomas. The median age of the patients was 57 years (range, 27–71 years). The primary sites of involvement were the bladder, urethra, urachus, and ureter in 43%, 29%, 19%, and 10% of the patients, respectively. Adenocarcinoma was the most common histological type (67%); squamous cell carcinoma and small cell carcinoma comprised 24 and 10% of the histologic types, respectively. With a median duration of follow-up of 32 months (range, 12–71 months), the median overall survival for all 21 patients from the day of first-line chemotherapy was 13 months (95% CI, 6.8–19.2). The expected 1-year survival rate was 50.6% (95% CI, 28.6–72.5). Univariate analysis showed a better median overall survival in patients with adenocarcinoma, compared to non-adenocarcinomas (47 vs. 10 months, P = 0.049). The median overall survival of patients who received platinum-based palliative chemotherapy for advanced non-transitional cell carcinomas was comparable to previous studies for patients with transitional cell carcinomas. Adenocarcinomas appear to have a favorable prognosis for the survival of the patients who received platinum-based chemotherapy for advanced non-transitional cell carcinomas.     

Retrospective analysis of third-line and fourth-line chemotherapy for advanced non-small-cell lung cancer

BackgroundThe efficacy of third-line and further-line chemotherapy for advanced non–small-cell lung cancer (NSCLC) remains unknown.Patients and MethodsWe evaluated the clinical outcome of third- and fourth-line chemotherapy for the treatment of advanced NSCLC in consecutive patients who received first-line chemotherapy at our institute between July 2002 and June 2006. From a hospital-based registry, the following data were extracted: (a) patient characteristics, (b) type of chemotherapeutic agents, and (c) objective response and survival data.ResultsA total of 599 patients were included in this analysis. Overall, 69.3%, 38.4%, 17.7%, and 6.0% of the patients received second-, third-, fourth-, and fifth-line chemotherapy, respectively. Significant differences in age (P < .0001), performance status at the start of first-line chemotherapy (P < .0001), and histology (P = .0175) were observed between patients who received third-line chemotherapy and those who did not. Docetaxel, gefitinib, and S-1 were the most frequently used regimens for third- or fourth-line chemotherapy. Five percent of the patients had participated in phase I trials of investigational new drugs. The objective response rates and disease control rates of third- and fourth-line chemotherapy were 17.0% and 34.4% and 11.3% and 24.5%, respectively. The median survival times (95% confidence interval [CI]) from the start of first-, second-, third-, and fourth-line chemotherapy until death were 15.3 months (95% CI, 13.8-16.5 months), 12.8 months (95% CI, 10.7-14.5 months), 12.0 months (95% CI, 9.3-14.2 months), and 9.9 months (95% CI, 8.6-12.0 months), respectively.ConclusionAs many as 38% of patients with advanced NSCLC who received first-line chemotherapy could receive third-line chemotherapy. This result emphasizes the need for randomized controlled trials of third-line treatment in patients with advanced NSCLC.     

High response of second-line chemotherapy with pemetrexed or gemcitabine combined with carboplatin in patients with non-small-cell lung cancer experiencing progression following 6 months after concluding platinum-based chemotherapy

Because of improved therapeutic results after first-line platinum-based chemotherapy in patients with stage IV non-small-cell lung cancer (NSCLC), second-line chemotherapy may be considered for a growing number of patients. Approximately, 10% of patients have an interval time after concluding first-line platinum-based chemotherapy greater than 6 months. These patients may achieve high tumor responses when platinum is again used in second-line treatment. Twenty-three patients experiencing progression following 6 months after concluding platinum-based chemotherapy were managed with second-line treatment with carboplatin combined with gemcitabine or pemetrexed. Overall response, progression-free survival (PFS), and overall survival (OS) after initiation of second-line treatment were calculated for all patients. Median PFS after first-line treatment was 12.6 months (95% confidence interval [95% CI], 10.4–14.7 months). Partial response was achieved in 7 of 23 patients, resulting in an overall response of 30.4% (95% CI, 11.6–49.0). Following initiation of second-line chemotherapy, median PFS was 5.9 months (95% CI, 1–10.9 months) and median OS was 12.5 months (95% CI, 3.5–21.5 months). The 1-year survival rate for all patients was 61.0% (95% CI, 29.5–82.0). Adding these results to those of the 10 previously published trials, 75 of 326 patients, 23%, (95% CI, 18.7–27.3) presented an overall response with the use of second-line platinum-based chemotherapy. The use of platinum combinations as second-line chemotherapy seems to have a place in the management of patients with advanced NSCLC, especially those with an interval time to progression greater than 6 months.     

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.     

Platinum-based chemotherapy in triple-negative breast cancer

BackgroundExperimental data suggest that triple-negative (TN) breast cancer may have increased sensitivity to platinum-based chemotherapy but clinical data are limited. We present our long-term results with platinum-based chemotherapy for TN breast cancer.Patients and methodsIn all, 94 (17 TN), 79 (11 TN) and 155 (34 TN) patients receiving platinum-based chemotherapy in neo-adjuvant/adjuvant and advanced setting were included. Response rates and outcome were compared for TN tumours versus others.ResultsNeo-adjuvant complete response rates were significantly higher for TN tumours (88%) than others (51%; P = 0.005). The 5-year overall survival (OS) for TN tumours following adjuvant/neo-adjuvant chemotherapy was 64% [95% confidence interval (CI) 44% to 79%] compared with 85% (95% CI 79% to 90%) for others. Five-year disease-free survival for TN tumours was 57% (95% CI 37% to 73%) compared with 72% (95% CI 64% to 78%) for others. For patients with advanced breast cancer, overall response rates were 41% for TN tumours and 31% for others (P = 0.3). Patients with TN tumours had a significantly prolonged progression-free survival of 6 months compared with 4 months for others (P = 0.05), though the OS was not significantly different between the two groups (11 versus 7 months).ConclusionPlatinum-based chemotherapy achieves increased response rates for TN tumours, with a trend towards worse survival in early breast cancer through an improved survival in advanced disease. Prospective randomised trials are warranted.     

Approval summary: erlotinib maintenance therapy of advanced/metastatic non-small cell lung cancer (NSCLC)

On April 16, 2010, the U. S. Food and Drug Administration (FDA) approved erlotinib tablets (Tarceva®; OSI Pharmaceuticals, Inc., Melville, NY) for maintenance treatment of patients with stage IIIB/IV non-small cell lung cancer (NSCLC) whose disease had not progressed after four cycles of platinum-based first-line chemotherapy.In total, 889 patients received either erlotinib (150 mg) or placebo once daily. Progression-free survival (PFS), in all patients and in patients with epidermal growth factor receptor (EGFR)⁺ tumors by immunohistochemistry (IHC), was the primary efficacy endpoint. Overall survival (OS) was a secondary sponsor endpoint but was the primary regulatory endpoint.Median PFS times were 2.8 months and 2.6 months in the erlotinib and placebo arms, respectively (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.62–0.82; p < .001). Median OS times were 12.0 months and 11.0 months, favoring erlotinib (HR, 0.81; 95% CI, 0.70–0.95). The PFS and OS HRs in patients with EGFR⁺ tumors by IHC were 0.69 (95% CI, 0.58–0.82) and 0.77 (95% CI, 0.64–0.93), respectively. The PFS and OS HRs in patients with EGFR⁻ tumors by IHC were 0.77 (95% CI, 0.51–1.14) and 0.91 (95% CI, 0.59–1.38), respectively.Following disease progression, 57% of placebo-treated patients received additional chemotherapy, compared with 47% of erlotinib-treated patients. Fourteen percent of placebo-treated patients received erlotinib or gefitinib, 31% received docetaxel, and 14% received pemetrexed. In total, 59% of placebo-treated patients who received treatment received FDA approved second-line NSCLC drugs.The most common adverse reactions in patients receiving erlotinib were rash and diarrhea.     

Prognostic Implications of Mucinous Differentiation in Metastatic Colorectal Carcinoma Can Be Explained by Distinct Molecular and Clinicopathologic Characteristics

Background

The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remains poorly characterized. The present study characterized the baseline characteristics, mutational profile, and clinical outcomes of patients diagnosed with mucinous CRC.

Statin therapy and association with ovarian cancer risk in the New England Case Control (NEC) study

Statins are widely used to lower blood cholesterol and reduce risk for cardiovascular diseases, but attention has recently focused on a role in cancer prevention or therapy. Here we present data from a large case–control study addressing whether statin use can lower the risk for epithelial ovarian cancer (EOC). Between 1992 and 2008, data including medications used for at least 6 months were collected from 2,040 cases with EOC and 2,100 frequency-matched controls without the disease who participated in the New England Case Control study. We used unconditional logistic regression controlling for matching factors and potential confounders to examine the association between statin use and the risk for EOC. Overall, women who used statins had 32% lower risk of ovarian cancer compared to non-users (Odds ratio (OR) 0.68, 95% Confidence Interval (CI): 0.54–0.85), adjusting for the matching factors and other covariates. The reduced risk was most apparent in women taking a lipophilic statin who began use after age 49, and who had used them 2–4.9 years. Statin use was associated with lower risks for both serous and non-serous histologic subtypes with the strongest effect seen for mucinous and mixed epithelial subtypes. The association became apparent about a decade after the introduction of statins and did not appear to be confounded by indications for use of statins or medications used concomitantly. In this case–control study, statins were found to lower the risk for both serous and non-serous EOC and especially mucinous EOC.     

A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial

BackgroundWe sought to determine whether the substantial benefits of topical nitroglycerin with first-line, platinum-based, doublet chemotherapy in advanced nonsmall-cell lung cancer (NSCLC) seen in a phase II trial could be corroborated in a rigorous, multicenter, phase III trial.Patients and methodsPatients starting one of five, prespecified, platinum-based doublets as first-line chemotherapy for advanced NSCLC were randomly allocated treatment with or without nitroglycerin 25 mg patches for 2 days before, the day of, and 2 days after, each chemotherapy infusion. Progression-free survival (PFS) was the primary end point.ResultsAccrual was stopped after the first interim analysis of 270 events. Chemotherapy was predominantly with carboplatin and gemcitabine (79%) or carboplatin and paclitaxel (18%). The final analysis included 345 events in 372 participants with a median follow-up of 33 months. Topical nitroglycerin had no demonstrable effect on PFS [median 5.0 versus 4.8 months, hazard ratio (HR) = 1.07, 95% confidence interval (CI) 0.86–1.32, P = 0.55], overall survival (median 11.0 versus 10.3 months, HR = 0.99, 95% CI 0.79–1.24, P = 0.94), or objective tumor response (31% versus 30%, relative risk = 1.03, 95% CI 0.82–1.29, P = 0.81). Headache, hypotension, syncope, diarrhea, dizziness, and anorexia were more frequent in those allocated nitroglycerin.ConclusionThe addition of topical nitroglycerin to carboplatin-based, doublet chemotherapy in NSCLC had no demonstrable benefit and should not be used or pursued further.Clinical Trials NumberAustralian New Zealand Clinical Trials Registry Number ACTRN12608000588392.     

International Collaborative Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma

BACKGROUND: Adjuvant chemotherapy has been suggested as a possible strategy to improve survival in women with early-stage ovarian cancer; however, all randomized studies to date have been too small to answer this question reliably. METHODS: We performed a preplanned combined analysis of two parallel randomized clinical trials (International Collaborative Ovarian Neoplasm 1 [ICON1] and Adjuvant ChemoTherapy In Ovarian Neoplasm [ACTION]) in early-stage ovarian cancer that compared platinum-based adjuvant chemotherapy with observation following surgery. Between November 1990 and January 2000, 925 patients (477 in ICON1 and 448 in ACTION) who had surgery for early-stage ovarian cancer were randomly assigned to receive platinum-based adjuvant chemotherapy (n = 465) or observation (n = 460) until chemotherapy was indicated. Kaplan-Meier analysis was used to compare overall and recurrence-free survival by treatment allocation. In subgroup analyses of pretreatment age, tumor stage, histologic cell type, and differentiation grade, the differences in relative size of effect were tested using a chi-square test for interaction or a chi-square test for trend. All tests of statistical significance were two-sided. RESULTS: After a median follow-up of over 4 years, 245 patients had died or had a recurrence (ICON1: 133, ACTION: 112). Overall survival at 5 years was 82% in the chemotherapy arm and 74% in the observation arm (difference = 8% [95% confidence interval (CI) = 2% to 12%]; hazard ratio [HR] = 0.67, 95% CI = 0.50 to 0.90; P =.008). Recurrence-free survival at 5 years was also better in the adjuvant chemotherapy arm than it was in the observation arm (76% versus 65%, difference = 11% [95% CI = 5% to 16%]; HR = 0.64, 95% CI = 0.50 to 0.82; P =.001). Subgroup analyses provided no evidence of a difference in the size of effect of chemotherapy on survival in any pretreatment subcategory. CONCLUSIONS: Platinum-based adjuvant chemotherapy improved overall survival and recurrence-free survival at 5 years in this combined group of patients with early-stage ovarian cancer defined by the inclusion criteria of the ICON1 and ACTION trials.     

DiM: Prognostic Score for Second- or Further-line Immunotherapy in Advanced Non–Small-Cell Lung Cancer: An External Validation

BackgroundOther than the programmed cell death ligand 1 (PD-L1) value, oncologists have only the clinical characteristics of patients with advanced non–small-cell lung cancer (aNSCLC) to determine candidates for immunotherapy. A clinical prognostic score composed of the Eastern Cooperative Oncology Group performance status, sex, histologic type, stage, platinum-based first-line therapy, and response to first-line therapy has categorized 3 prognostic groups for patients undergoing second-line chemotherapy. We sought to validate the same score for patients with aNSCLC treated with second- or further-line immunotherapy.Materials and MethodsWe collected data from 2 Italian centers. A score was generated to divide patients into 3 prognostic groups: best, score < 5; intermediate, score 5 to 9; and worst, score > 9. Overall survival (OS) and progression-free survival (PFS) were the endpoints.ResultsA total of 347 patients were included for analysis. Their median age was 66 years (range, 30-88 years), most were aged < 70 years (67.5%), 70.7% were men, 79.5% were smokers, and 74.6% had had adenocarcinoma. The Eastern Cooperative Oncology Group performance status was 0 for 23%, 1 for 54.5%, and 2 for 22.5%. Of the 347 patients, 28% were in the best prognosis, 51% in the intermediate, and 21% in the worst prognosis group, respectively. The median OS was 18.0 months for the best, 8.5 months for the intermediate (hazard ratio [HR] vs. best, 1.83; 95% confidence interval [CI], 1.35-2.47; P < .001) and 2.6 months for worst (HR vs. best, 5.77; 95% CI, 3.99-8.33; P < .001) group. The median PFS was 3.4 months for the best, 3.7 months for the intermediate (HR vs. best, 1.35; 95% CI, 1.03-1.77; P = .032), and 1.9 months for the worst (HR vs. best, 2.51; 95% CI, 1.80-3.50; P < .001) group.ConclusionsThe prognostic score was able to predict the outcomes of patients with aNSCLC who had received immunotherapy. The worst category showed a dismal life expectancy and probably would not benefit from active systemic therapy. Thus, for these patients, best supportive care could be the best choice.     

Impact of intraoperative rupture of the ovarian capsule on prognosis in patients with early-stage epithelial ovarian cancer: A meta-analysis

Background

The impact of intraoperative rupture on prognosis is controversial in early-stage epithelial ovarian cancer (EOC). Thus, we performed a meta-analysis to determine its impact and to evaluate factors to increase its risk.

Methods

We searched PubMed, Embase, and the Cochrane Library till May 2011, and 9 eligible studies including 2382 patients were evaluated. All patients were classified into three groups: no rupture; intraoperative rupture; preoperative involvement.

Results

Preoperative involvement decreased progression-free survival when compared with intraoperative rupture (PFS; HR, 1.47; 95% CI, 1.01–2.14), which also showed poorer PFS than no rupture (HR, 2.41; 95% CI, 1.74–3.33). Although preoperative involvement reduced PFS when compared with intraoperative rupture (HR, 2.63; 95% CI, 1.11–6.20), there was no difference in it between intraoperative rupture and no rupture in patients who underwent complete surgical staging operation and adjuvant platinum-based chemotherapy if needed (HR, 1.49; 95% CI, 0.45–4.95). Furthermore, adhesion to adjacent tissues, grade 2 or 3 disease were more common (ORs, 2.01 and 2.47; 95% CIs, 1.20–3.37 and 1.12–5.46), whereas mucinous tumor was less frequent (OR, 0.51; 95% CI, 0.37–0.72) in intraoperative rupture than in no rupture.

Conclusions

Intraoperative rupture may not decrease PFS when compared with no rupture in patients with early-stage EOC who underwent complete surgical staging operation and adjuvant platinum-based chemotherapy. Furthermore, more adhesion to adjacent tissues and grade 2 or 3 disease, and less mucinous tumor are expected to increase the risk of intraoperative rupture.     

KRAS-specific Amino Acid Substitutions are Associated With Different Responses to Chemotherapy in Advanced Non–small-cell Lung Cancer

Background

Emerging data highlight different clinical behaviors according to KRAS amino acid substitutions (AASs) in patients with non–small-cell lung cancer (NSCLC). We aimed to evaluate whether different KRAS AASs were associated with different responses to chemotherapy.

Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC cohort study

New data regarding a positive association between smoking and risk of epithelial ovarian cancer (EOC), especially the mucinous tumor type, has started to emerge. The purpose of this study was to examine the association between different measures of smoking exposures and subtypes of EOC in a large cohort of women from 10 European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort is a multicenter prospective study initiated in 1992. The questionnaires included data about dietary, lifestyle, and health factors. Information about cigarette smoking was collected from individuals in all participating countries. We used Cox proportional hazard regression models to estimate hazard ratio (HR) of EOC overall and serous, mucinous, and endometroid histological subtypes, with 95% confidence intervals (CIs) associated with different measures of smoking exposures adjusting for confounding variables. Altogether 836 incident EOC cases were identified among 326,831 women. The tumors were classified as 400 serous, 83 mucinous, 80 endometroid, 35 clear cell, and 238 unspecified. Compared with never smokers, current smokers had a significantly increased risk for mucinous tumors [HR = 1.85 (95% CI 1.08-3.16)] and those smoking more than 10 cigarettes per day had a doubling in risk [HR = 2.25(95% CI 1.26-4.03)] as did those who had smoked less than 15 pack-years of cigarettes [HR = 2.18 (95% CI 1.07-4.43)]. The results from the EPIC study add further evidence that smoking increases risk of mucinous ovarian cancer and support the notion that the effect of smoking varies according to histological subtype.     

Treatment of Metastatic Urothelial Carcinoma After Previous Cisplatin-based Chemotherapy for Localized Disease: A Retrospective Comparison of Different Chemotherapy Regimens

BackgroundOptimal chemotherapy for patients who received cisplatin for localized urothelial carcinoma (UC) and develop metastatic disease is unclear. We compared the efficacy of platinum-based (PBC) versus non–platinum-based (NPBC) first-line chemotherapy for metastasis.Patients and MethodsData were collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database of 3024 patients from 28 international academic centers from 2005 to 2012. Patient inclusion criteria included: (1) predominant UC; (2) any primary tumor site; (3) cT2-4, cN0-N2, cM0; (4) prior receipt of perioperative/radiation cisplatin-containing chemotherapy; and (5) receipt of cytotoxic chemotherapy in the first-line metastatic setting. Multivariate Cox proportional hazards models were used to show progression-free survival (PFS) and overall survival (OS) from the first day of chemotherapy for metastatic disease to date of censor.ResultsEligibility criteria was met by 132 patients (n = 74 PBC; n = 58 NPBC). The median OS was 8.13 months (interquartile range, 4.87-16.64 months) and 8.77 months (interquartile range, 4.01-13.49 months) for PBC and NPBC, respectively. Neither OS (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.64-1.69; P = .87) nor PFS (HR, 0.86; 95% CI, 0.56-1.31; P = .48) differed for PBC versus NPBC. However, for patients who received chemotherapy more than a year after perioperative/radiation chemotherapy, OS was superior for PBC over NPBC (HR, 0.31; 95% CI, 0.10-0.92; P = .03).ConclusionsThere is no significant outcome difference between PBC and NPBC in patients with metastatic UC who previously received cisplatin-based chemotherapy for localized disease. However, if over a year has elapsed, return to PBC is associated with superior OS.     

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.     

Retrospective analysis of carboplatin and paclitaxel as initial second-line therapy for recurrent epithelial ovarian carcinoma: application toward a dynamic disease state model of ovarian cancer.

PURPOSE: The majority of patients with epithelial ovarian cancer (EOC) who achieve a complete remission with front-line chemotherapy develop recurrent disease. Carboplatin and paclitaxel are used for patients with platinum-sensitive recurrent disease, although there is little information regarding the response and survival in unselected patients treated with this strategy. We sought to determine the outcomes for patients with EOC treated with carboplatin and paclitaxel at the time of first recurrence. In addition, we sought to define a new paradigm for disease transition in patients with EOC. PATIENTS AND METHODS: Eighty-nine patients were identified who had a complete response to front-line platinum-based chemotherapy for EOC, relapsed 6 months after completion of front-line chemotherapy, and were treated with carboplatin and paclitaxel as second-line therapy. RESULTS: Eighty-four cases were available for analysis of survival end points, and 66 were assessable for response. The median follow-up was 27 months. The overall response rate was 70%. The median progression-free interval for the cohort was 13 months (95% confidence interval [CI], 10.7 to 13.8 months). The 3-year survival rate was 72% (95% CI, 59.4 to 86.1%). Toxicity was limited, and no deaths from treatment were observed. Using this data, it is possible to construct a disease states model of EOC, which provides risk estimates for transitions between clinically distinct categories. CONCLUSION: Re-treatment with carboplatin and paclitaxel is effective as initial therapy in recurrent EOC. This should form the basis of a randomized trial to determine the best agents for initial treatment of relapse from EOC in potentially platinum-sensitive patients.     

Hormone replacement therapy and the risk of invasive epithelial ovarian cancer in Swedish women

BACKGROUND: Estrogen replacement therapy (ERT), which is mainly used to relieve climacteric symptoms, increases a woman's risk for uterine endometrial cancer and epithelial ovarian cancer (EOC). Estrogens are often combined with progestins in hormone replacement therapy (HRT) to reduce the risk of uterine endometrial cancer. Data on the association between HRT including progestins and EOC risk are limited. This nationwide case-control study examined EOC risk in relation to HRT regimens with sequentially added progestins (HRTsp) and continuously added progestins (HRTcp). METHODS: Between 1993 and 1995, we enrolled 655 histologically verified incident case patients with EOC and 3899 randomly selected population controls, all 50-74 years of age. Data on HRT use were collected through mailed questionnaires. Multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by the use of unconditional logistic regression. RESULTS: Risks of EOC were elevated among ever users as compared with never users of both ERT (OR = 1.43, 95% CI = 1.02 to 2.00) and HRTsp (OR = 1.54, 95% CI = 1.15 to 2.05); risks were elevated for serous, mucinous, and endometrioid subtypes. For all EOC types combined, the greatest risk increases were seen with hormone use exceeding 10 years. Ever use of HRTcp was not associated with increased EOC risk relative to HRTcp never use (OR = 1.02, 95% CI = 0.73 to 1.43). The risk of EOC was elevated among HRTsp ever users as compared with HRTcp ever users (OR = 1.78, 95% CI = 1.05 to 3.01). ORs for EOC after ever use of low-potency estrogens were 1.18 (95% CI = 0.89 to 1.55) for oral and 1.33 (95% CI = 1.03 to 1.72) for vaginal applications, but no relationship was seen between EOC risk and duration of use. CONCLUSION: Ever users of ERT and HRTsp but not HRTcp may be at increased risk of EOC.