Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect. VEGF levels are prognostic for PFS and OS in RCC. The results of TARGET establish the efficacy and safety of sorafenib in advanced RCC.

We report the results of the Ticlopidine Aspirin Stroke Study, a blinded trial at 56 North American centers that compared the effects of ticlopidine hydrochloride (500 mg daily) with those of aspirin (1300 mg daily) on the risk of stroke or death. The medications were randomly assigned to 3069 patients with recent transient or mild persistent focal cerebral or retinal ischemia. Follow-up lasted for two to six years. The three-year event rate for nonfatal stroke or death from any cause was 17 percent for ticlopidine and 19 percent for aspirin--a 12 percent risk reduction (95 percent confidence interval, -2 to 26 percent) with ticlopidine (P = 0.048 for cumulative Kaplan-Meier estimates). The rates of fatal and nonfatal stroke at three years were 10 percent for ticlopidine and 13 percent for aspirin--a 21 percent risk reduction (95 percent confidence interval, 4 to 38 percent) with ticlopidine (P = 0.024 for cumulative Kaplan-Meier estimates). Ticlopidine was more effective than aspirin in both sexes. The adverse effects of aspirin included diarrhea (10 percent), rash (5.5 percent), peptic ulceration (3 percent), gastritis (2 percent), and gastrointestinal bleeding (1 percent). With ticlopidine, diarrhea (20 percent), skin rash (14 percent), and severe but reversible neutropenia (less than 1 percent) were noted. The mean increase in total cholesterol level was 9 percent with ticlopidine and 2 percent with aspirin (P less than 0.01). The ratios of high-density lipoprotein and low-density lipoprotein to total cholesterol were similar in both treatment groups. We conclude that ticlopidine was somewhat more effective than aspirin in preventing strokes in this population, although the risks of side effects were greater.

The 12% response rate for these patients was no greater than that observed for single-agent doxorubicin. However, the 65% of patients with stable disease lasting four cycles or longer suggests further study is warranted in STSs. The observed cardiac toxicity, despite close monitoring and standard use of dexrazoxane, obliges a change in the dose and/or schedule in future studies of this combination.

BackgroundThe perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy.MethodsThis retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age ≥70 years, n = 115) and younger patients (age <70 years, n = 787) who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease), time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportional hazards model. Kaplan–Meier analyses were used to summarize time-to-event data.ResultsMedian progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66) and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69). Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively) and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively). Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03) and younger patients (90 days with sorafenib vs 52 days with placebo; HR = 0.69, 95% CI = 0.59 to 0.81) and improved quality of life over that time.ConclusionsAmong patients with advanced renal cell carcinoma receiving sorafenib treatment, outcomes of older (≥70 years) and younger (<70 years) patients were similar.

YKL-40 may represent a novel marker for the detection of early-stage ovarian cancer. YKL-40 levels in early-stage patients may also predict disease recurrence and survival. The utility of YKL-40 in detection of early-stage ovarian cancer deserves further investigation.

BACKGROUND Benign uterine leiomyomata (LMA) are hormonally responsive neoplasms. To the authors' knowledge, little is known regarding the hormonal expression patterns of leiomyosarcomas (LMSs) of the uterus. The objective of the current study was to assess the immunohistochemical (IHC) patterns of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) expression in LMA and LMS of the uterus using a tissue microarray. The authors also sought to assess the prognostic value of ER, PR, and AR expression in LMS. METHODS Between January 1991 and March 2001, 25 patients were identified with primary uterine LMS for whom tissue was available. A tissue microarray was created with 3 representative cores from each of the LMS cases, as well as from 19 cases with benign uterine LMA. IHC staining was scored as follows: negative (0–1) and positive (2–3). Outcome analyses were performed for LMS only. First recurrence was determined from the time of the initial diagnosis. Survival was determined from the time of the initial diagnosis to last follow‐up. RESULTS ER, PR, and AR positivity in LMA compared with LMS was as follows: ER, 78% versus 40% (P = 0.03); PR, 88% versus 38% (P = 0.001); and AR, 32% versus 40% (P = 0.75). There was no difference noted with regard to IHC expression based on stage of LMS. The median overall survival for patients with LMS was 23.5 months (95% confidence interval, 19.5, NR). When adjusted for stage, PR and AR were found to be predictive of a lower risk of recurrence (P = 0.01 and P = 0.035, respectively). ER, PR, and AR were not found to be associated with overall survival after adjustment for stage. Tumor stage was found to be associated with survival (P = 0.005). CONCLUSIONS The rate of ER and PR expression was found to be significantly less in uterine LMS compared with LMA. ER, PR, and AR expression was observed in approximately 30–40% of uterine LMS cases. In the current series, PR and AR expression appeared to be associated with disease‐free survival but were not found to correlate with overall survival. Cancer 2004. © 2004 American Cancer Society.

We present a single institution experience with 5-FU, mitomycin-C based chemoradiation for the primary treatment of elderly patients with oesophageal cancer. Twenty-five patients with a median age of 77 years (range 66 -88) with a diagnosis of stage II -III squamous cell or adenocarcinoma of the oesophagus were treated at Memorial Sloan Kettering from 1996 to 2001 with two cycles of concurrent 5-FU, mitomycin-C and 50.4 Gy. Owing to age and comorbidity, these patients were not considered surgical candidates. The Charlson comorbidity score was used to evaluate patient comorbidity. Nine patients (36%) experienced grade 3 -4 haematologic toxicity. Of the 23 patients evaluable for response, 17 patients (68%) had a negative post-treatment endoscopy and CT scan without evidence of progressive disease. Eleven patients (44%) are alive and 10 (40%) remain without evidence of recurrent or progressive oesophageal cancer at a median follow-up of 35 months. The median overall survival was 35 months and 2-year survival 64%. There was no significant difference in overall survival between Charlson score p2 and those with a score X2 (P ¼ 0.10). Similar survival was observed for patients with adenocarcinoma or squamous carcinoma. Primary chemoradiation with two cycles of 5-FU, mitomycin-C, and 50.4 Gy in elderly patients is an active regimen with moderate toxicity, despite the advanced age and heavy comorbidity burden of this cohort. Patients with local/regional oesophageal cancer with adequate functional status should not be excluded from potentially curative treatment based on age alone.

CT-2103 is active in patients with recurrent ovarian cancer. Neurotoxicity in these heavily pretreated patients was more frequent than predicted from phase I trials. Further study to define toxicity and efficacy in patients with less prior therapy is ongoing.