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Purpose Outcome data on hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) nonamplified (HER2−) metastatic breast cancer (MBC) treated with palbociclib after treatment with everolimus are lacking. The PALOMA-3 trial, showing benefit of palbociclib plus fulvestrant compared to fulvestrant alone in HR+HER2− MBC after progression while receiving endocrine therapy excluded women previously treated with everolimus. The objective of this study was to examine outcomes of HR+HER2− MBC with prior exposure to everolimus while receiving palbociclib-based therapy. Patients and Methods A retrospective, single-institute review was conducted of HR+HER2− MBC from January 2014 to November 2016 in patients treated with palbociclib after prior treatment with everolimus. Progression-free survival (PFS) was defined as the time from initiation of palbociclib to the date of progression as determined by the treating physician based on radiologic, biochemical, and/or clinical criteria. Response rates were determined on the basis of available radiologic data. Objective response rate (ORR) was defined as the rate of any complete or partial responses; clinical benefit rate (CBR) was the rate of complete response, partial response, or stable disease for at least 24 weeks. Results Twenty-three patients with a mean (range) age of 68 (42-81) years were identified. Kaplan-Meier estimate showed median PFS of 2.9 months (95% confidence interval, 2.1-4.2); ORR was 0 of 23 and CBR was 4 (17.4%) of 23. In the PALOMA-3 trial, median PFS, ORR, and CBR of palbociclib cohort were 9.5 months (95% confidence interval, 9.2-11.0), 19%, and 67%, respectively. Conclusion There is a limited clinical activity of palbociclib combinations after progression with everolimus combination therapy. Further studies are necessary to confirm these findings.

Background Recent studies suggest that older women derive similar benefits from adjuvant systemic chemotherapy (AST) as younger women. In older women, the ability to successfully complete chemotherapy may be complicated by other health conditions and performance status. We examined factors affecting the delivery of chemotherapy to older patients with breast cancer. Methods Women age ≥ 65 treated with adjuvant/neoadjuvant chemotherapy at Roswell Park Cancer Institute were identified from the RPCI database from 7/1997 to 4/2010. Endpoints were delay, hospitalization, dose reduction, relative dose intensity (RDI) Results 204 older women received AST. Median follow-up was 50.2 months. Seventy percent received anthracycline-based AST. In multivariate analysis, older age was a predictor for early termination of chemotherapy and RDI Conclusion Successful administration of planned chemotherapy to older women with breast cancer was associated with improved OS. However, delivery of chemotherapy was associated with increased toxicity and reduced tolerance. Models allowing physicians to better risk-stratify older patients with breast cancer are needed and under development.

At present, a combination of cisplatin, methotrexate, vinblastine and doxorubicin is the most widely used chemotherapy for metastatic bladder cancer. However, long-term follow-up shows that this combination may have little effect on survival. In addition, this regimen is toxic. New agents are needed which combine efficacy with good safety profiles. Agents which have been investigated include gallium nitrate, interferon-alpha and paclitaxel both as single agents and in combination with established cytotoxic drugs. A number of studies have been conducted in bladder cancer with the novel nucleoside analogue, gemcitabine. Response rates of up to 33% have been recorded in two phase II studies. Gemcitabine was well tolerated in both studies with few of the side-effects normally associated with cytotoxic drugs. A third study is ongoing.

Gemcitabine is a nucleoside analogue with broad-spectrum activity in several solid tumours. In a Phase I trial, responses were seen in patients with MVAC-refractory bladder cancer. Currently 21 patients with no prior chemotherapy for metastatic transitional cell cancer have been entered on a Phase II trial of gemcitabine at 1200 mg/m2 weekly × 3 every 4 weeks. Patient characteristics include 14 males, 7 females; median age 71 (range 42–88), median Karnofsky performance status 80 (range 60-100); 20 metastatic, 1 locally advanced disease; 2 prior adjuvant or neoadjuvant chemotherapy and 2 with prior radiation therapy. Currently 18 patients are evaluable for response with 3 too early. There have been 11 partial responses among the 18 evaluable patients. Sites of response have included pelvic and periaortic lymph nodes, liver and lung metastases. Toxicity has been modest in this study with no Grade 4 drug-related side effects. Grade 3 nausea and vomiting have been encountered as have Grade 1 and 2 leukopenia, myalgias, skin rash and fever. One patient with a partial response developed pneumocystis pneumonia with lowered T-4 counts and was removed from study. When he subsequently progressed (approximately 5 months later) he was retreated with gemcitabine (and trim-sulfa prophylaxis) and again has had a partial response. These data suggest that gemcitabine has promising activity in patients with transitional cell cancer and merits combination studies with other active agents in this disease such as cisplatin (with which preclinical synergy has been demonstrated) and paclitaxel.

Glucocortoid receptor (GR) levels have not been extensively studied in untreated patients with chronic lymphocytic leukemia (CLL). We have measured tumor GR levels using a whole cell assay in 18 untreated patients with CLL and correlated these levels with various in-vitro and in-vivo data. In 12 of these patients, tumor cells from more than one tissue were simultaneously studied. Measurable GR levels were found in all 36 specimens studied with median total GR levels in blood, bone marrow, and lymph nodes being 3018 (n = 17), 3524 (n = 12) and 3102 (n = 7) sites/cell respectively. GR levels did not correlate with in-vitro sensitivity, as measured by inhibition by dexamethasone of radiolabelled leucine, uridine, and thymidine uptake, nor with the clinical or laboratory features examined. Nine patients were treated with dexamethasone as a single agent; blood GR levels were not predictive of antitumor response. We conclude that in patients with CLL, malignant cells from all involved tissues have measurable numbers of GRs, but these are not correlated with in-vitro sensitivity to glucocorticoid. Blood GR levels do not correlate with antitumor response; further studies are required to see if bone marrow or lymph node receptor levels correlate with antitumor response to steroids.