Cyclin-dependent kinase 4/6 inhibitors in the treatment of advanced or metastatic breast cancer.

OBJECTIVE: Despite the relatively high cure rates in early-stage breast cancer, advanced and metastatic breast cancer cases are associated with more inauspicious patient outcomes. Fortunately, with the advent of cyclin-dependent kinase (CDK)4/6 inhibitors (e.g. palbociclib, ribociclib, and abemaciclib) with endocrine therapy, survival in advanced and metastatic breast cancer has appreciably improved. In the current review, we discuss these distinctions and the concomitant implications associated with the individual CDK4/6 inhibitors. DATA SOURCES: We conducted an extensive PubMed search comprising several review articles on the topic of advanced or metastatic breast cancer treatment, with specific terms that included CDK4/6 inhibitors, treatment, and breast cancer. DATA SUMMARY: Palbociclib, ribociclib, and abemaciclib have exhibited superior progression-free survival differences compared to endocrine therapy alone. However, there are differences among the various CDK4/6 inhibitors with regard to overall survival, tolerability and quality of life. CONCLUSIONS: Ribociclib may be indicated for pre/perimenopausal patients, whereas abemaciclib is potentially recommended to address endocrine-resistant or visceral disease. Alternatively, palbociclib is associated with lower discontinuation rates than abemaciclib and unlike ribociclib, QTc prolongation is not observed with palbociclib.

Current analysis of the survival implications for minimally invasive surgery in the treatment of early-stage cervix cancer.

Early-stage cervical cancer (ESCC) is managed with radical hysterectomy, a procedure that can be performed either via open surgery or minimally invasive surgery (MIS), the latter of which is accomplished via traditional laparoscopy or robotic-assisted surgery. Previously, MIS was routinely incorporated into the management of ESCC due to the approach's reduced operative morbidity and truncated hospital stay duration, but more recent clinical evidence has since impugned the efficacy of MIS because of the reportedly inferior disease-free survival and overall survival outcomes compared to open surgery. However, additional studies have documented equivalent outcomes among the various surgical modalities, suggesting further exploration of clinical factors as we endeavor to conclusively determine the standard of care for patients diagnosed with ESCC.

Prolonged endocrine therapy in the management of hormone receptor-positive early-stage breast cancer: What is the appropriate duration?

AIM: The clinical benefits associated with 5 years of endocrine therapy in the treatment of hormone receptor-positive, early-stage breast cancer (ESBC) have been well-substantiated. However, numerous studies have reported on the results of extended (i.e., >5 years) endocrine therapy to further effectuate a clinical benefit, with varying outcomes. Hence, the purpose of this study is to review these prolonged investigations and endeavor to clarify their corresponding treatment implications. METHODS: We reviewed the study findings from several randomized controlled trials and meta-analyses, which incorporated clinical outcomes from pre-and postmenopausal, hormone receptor-positive, ESBC patients. RESULTS: Hormone receptor-positive, ESBC patients treated with 5 years of endocrine therapy, who are node-negative with tumors <2 cm, will unlikely benefit from five additional years of treatment. Conversely, in women with larger tumors and node-positive disease, 7-8 total years of endocrine therapy may be indicated. Ultimately, clinicians should also consider the attendant side effects from endocrine therapy, namely bone fractures, namely cardiovascular symptoms, and vasomotor symptoms, when considering the appropriate treatment regimen. CONCLUSIONS: While increased duration of endocrine therapy may selectively accord significant clinical benefits, prior to determining the patient's treatment interval, physicians should also assess the cumulative side effects from endocrine therapy when endeavoring to maintain treatment compliance and bolster quality of life.

A phase II, open-label, non-randomized, prospective study assessing paclitaxel, carboplatin and metformin in the treatment of advanced stage ovarian carcinoma.

OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of a paclitaxel, carboplatin and metformin regimen in the first-line treatment of advanced-stage ovarian, fallopian tube, and primary peritoneal carcinoma. METHODS: Eligible subjects underwent surgery and 6 cycles of neoadjuvant or adjuvant dose-dense intravenous paclitaxel (80 mg/m²), carboplatin (area under the curve 5 or 6 on Day 1), and oral metformin (850 mg daily). Study participants who completed their primary therapy and attained a clinically defined complete or partial response (PR) were treated with a planned 12 cycles of paclitaxel (135 mg/m² every 21 days) and metformin (850 mg twice daily) maintenance therapy. RESULTS: Thirty subjects received a median of 6 cycles (range, 5-6) of primary induction chemotherapy and were eligible for response evaluation; twenty-three patients exhibited a complete response, while 3 study patients obtained a PR (an overall response rate of 86.7%). Grade 3-4 hematological toxicity included neutropenia (43.3%), thrombocytopenia (10%) and anemia (36.7%). There was no incidence of grade 3-4 neuropathy although 15 patients (50%) developed grade ≤2 neurotoxicity. Additionally, we observed grade ≤2 diarrhea in 20 (66.7%) subjects. The median progression-free survival was 21 months (range, 3-52) and overall median survival was 35 months (range, 15-61). The subjects also received an aggregate 103 cycles (median, 12; range, 6-12) of maintenance chemotherapy. CONCLUSION: The study results suggest that the combination of paclitaxel, carboplatin and metformin is associated with moderate efficacy and a reasonable toxicity profile.

Hormone Therapy and Risk of Breast Cancer: Where Are We Now?

Several studies have examined the clinical benefits of hormone replacement therapy (HRT). However, because long-term use of HRT has been implicated as a risk factor for the development of breast cancer, some women remain skeptical when considering this therapy to address their vasomotor symptoms. Hence, physicians and nurses should actively engage in constructive discourse with their patients regarding HRT while specifically reviewing the potential risks of its extended use as well as provide the available medical alternatives the patients could potentially use.

Robotic-Assisted Surgery for the Treatment of Breast and Cervical Cancers.

Background: Robotic-assisted surgery facilitates the performance of numerous, complex procedures, namely conferring precision, flexibility, and control that is otherwise unavailable with conventional laparoscopy; and compared to open surgery, robotic-assisted surgery is ostensibly associated with fewer complications, reduced intraoperative complications, and shorter hospital stay duration. Nevertheless, the American College of Obstetricians and Gynecologists and the Food and Drug Administration have criticized the pervasive acceptance of robotic-assisted surgery, given the absence of randomized clinical trial data compared to traditional laparoscopy and open procedures, not to mention the increased surgical cost. Conclusions: While the research data continue to be borne out, surgeons should exercise considerable discretion in selecting the surgical approach from which their patients would derive the greatest clinical benefit.

Talc powder and ovarian cancer: what is the evidence?

Talc is a desiccant that has been historically used as baby powder by numerous women to enhance their feminine hygiene. Talc has been identified in proximity to asbestos; accordingly, retrospective and case-control studies have implicated the role of talc use in the development of ovarian cancer, whereas prospective evaluations have not documented concordant findings. Moreover, the positive associations derived from case-control studies have been remote and the putative causal factors remain inconclusive. Consequently, one should be circumspect regarding the assertion that genital talc powder application induces ovarian cancer development.

A retrospective study comparing the efficacy of dose-dense chemotherapy, intraperitoneal chemotherapy and dose-dense chemotherapy with hyperthermic intraperitoneal chemotherapy in the treatment of advanced stage ovarian carcinoma.

OBJECTIVES: Hyperthermic intraperitoneal chemotherapy (HIPEC), intraperitoneal chemotherapy (IP) and dose-dense (DD) chemotherapy have been employed with varying success in the treatment of advanced stage ovarian carcinoma. Despite the clinical benefits associated with these specific forms of chemotherapy administration, they have not been comparatively analyzed, vis-à-vis their efficacy. STUDY DESIGN: Advanced stage ovarian cancer patients who were treated with platinum/taxane chemotherapy via a DD regimen (n = 100), IP approach (n = 81) or a DD regimen in conjunction with HIPEC (n = 64) were retrospectively evaluated. The clinical variables of interest were patient age, body mass index, surgery and pathology data, chemotherapy regimen, inclusion of maintenance therapy, and progression free/overall survival. RESULTS: Progression free survival (PFS) was significantly more pronounced in the HIPEC (34.9 months) and IP (34.0 months) patients, compared to the DD group (27.6 months) (P = 0.005). A cox-proportional hazards regression model indicated that there was a decreased risk of disease progression accorded to the patients who were treated with IP chemo or HIPEC and DD chemotherapy (HR, 0.43; 95 % CI: 0.21-0.88; P = 0.022) and the subjects who underwent optimal cytoreductive surgery (HR, 2.42; 95 % CI: 1.22-4.80; P = 0.011). Positive BRCA status (HR, 0.434; 95 % CI: 1.59-3.44; P = 0.001) and number of chemotherapy regimens (HR, 1.36; 95 % CI: 1.159-1.61; P = 0.001) were significantly correlated with improved OS although we did not discern a survival benefit associated with any of the chemotherapy treatments (P = 0.136). CONCLUSION: We observed PFS advantages conferred to the ovarian cancer patients treated with HIPEC and IP chemotherapy compared to DD chemotherapy. However, an overall survival advantage related to the chemotherapy regimens was not borne out, possibly due to the retrospective nature of the study or differing time periods wherein the specific patient cohorts underwent treatment.

A Prospective, Observational Trial Assessing the Efficacy of Abdominal Compression in Reducing Laparoscopic-Induced Shoulder Pain.

INTRODUCTION: Postoperative shoulder pain is a condition associated with laparoscopic surgery and presumably attributed to residual carbon dioxide (CO2) in the abdomen. The intent of the current prospective, observational study was to assess the efficacy of abdominal compression in mitigating this painful complication. METHODS: We recruited 30 patients who were treated with laparoscopic surgery for the management of gynecologic disease. All study participants underwent abdominal compression to evacuate the CO2 associated with their pneumoperitoneum. Postoperatively, the subjects' pain intensity was measured via the visual analogue scale at 12, 24, and 48 hours. RESULTS: The patients' mean postoperative visual analogue scale pain scores were the highest during the initial 12 hours (1.93), and thereafter, steadily declined at 24 hours (0.73) and 48 hours (0.70) ( P = .045). Furthermore, toxicity was reasonable, with only 20% of subjects who reported grade ≤2 nausea and vomiting. CONCLUSION: Abdominal compression is a relatively safe procedure that appears to sufficently evacuate residual CO2, thereby reducing the severity of laparoscopic surgery induced shoulder pain.

Consolidation hyperthermic intraperitoneal chemotherapy for the treatment of advanced stage ovarian carcinoma: a 3 year experience.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) potentially confers significant survival benefits in the management of ovarian cancer although the long-term data remain scant. We sought to compare the survival rates of advanced stage ovarian cancer patients who were treated with primary induction therapy alone or in conjunction with consolidation HIPEC. METHODS: 69 ovarian cancer patients who underwent surgery and completed their primary induction chemotherapy were treated with consolidation carboplatin (AUC 10) based HIPEC and compared to a historical cohort that received surgery and primary chemotherapy alone (n = 69). The demographic and clinical characteristics on which we were primarily focused, included patient age, body mass index, surgery and pathology data, chemotherapy regimen, toxicity, and progression free/overall survival. RESULTS: The two patient groups' demographic and clinical characteristics were similar (P > 0.05). Progression-free survival was significantly more pronounced in the HIPEC (25.1 months) patients compared to the control group (20 months) (P = 0.024) and there was a decreased risk of disease progression accorded to the patients treated with HIPEC (HR 2.1028; 95% CI 1.2941-3.4167; P = 0.0027). However, we did not discern any HIPEC related overall survival advantages (P = 0.29). CONCLUSIONS: The results from our ovarian cancer study suggest that adjunctive HIPEC proffers a significant progression-free survival advantage and a decreased risk for disease progression. There was, however, no overall survival advantage discerned by the HIPEC group. We also recognize that HIPEC remains controversial, and thus randomized studies evaluating HIPEC compared to standard chemotherapy in the management of ovarian cancer are warranted.

The impact of total parenteral nutrition on postoperative recovery in patients treated for advanced stage ovarian cancer.

OBJECTIVES: Total parenteral nutrition (TPN) presumably benefits cancer patients although reports have disputed the significance of this nutritional intervention. We sought to compare the postoperative outcomes of ovarian cancer patients treated with either TPN or conservative management. METHODS: We retrospectively evaluated the impact of TPN and conservative management in ovarian cancer patients who underwent debulking surgery and a bowel resection. The primary study variables encompassed patient time until restoration of bowel function, number of postoperative complications and duration of hospital stay. RESULTS: There were 147 subjects who were selected for this study. The patients who were treated with TPN (n = 69) demonstrated a longer time until restoration of bowel function (5.77 vs. 4.70 days; P < 0.001), experienced lower pre-operative albumin levels (2.22 vs. 2.97 g/dL; P < 0.001) and endured a significantly longer hospital stay (11.46 vs. 7.14 days; P < 0.001) compared to the conservative management (n = 78) cohort. CONCLUSIONS: Postoperative TPN in ovarian cancer patients may be inadvisable because of the increased risk for complications. Moreover, in the hypoalbuminemic patients, TPN may have not only delayed their postoperative recovery and increased hospital stay duration, but further precipitated the manifestation of nosocomial sequelae.

Lower-extremity lymphedema following management for endometrial and cervical cancer.

BACKGROUND: Despite the alleged benefits conferred by a lymphadenectomy in the management of gynecologic malignancies, there are concerns regarding the development of postoperative lower-extremity lymphedema. The purpose of this study was to identify the incidence of lymphedema and associated risk factors in accordance with surgical staging during the management of endometrial and cervical cancer. METHOD: We conducted a 5-year review of all endometrial and cervical cancer patients who underwent a lymphadenectomy. The subjects' demographics, medical co-morbidities, diagnosis, surgical treatment, inclusion of adjuvant radiotherapy and incidence of lower-extremity lymphedema were noted. RESULTS: We identified 165 (135 endometrial cancer and 30 cervical cancer) subjects. Positive pelvic and para-aortic lymph nodes were present in 21 (12.7%) and 10 patients (6.1%), respectively. In the entire population, 6 (3.6% incidence) subjects developed post-operative lymphedema. Supplementary analyses revealed that a BMI >35 kg/m(2) and possessing numerous (≥3) co-morbidities significantly correlated with the manifestation of lower-extremity lymphedema. CONCLUSION: In the current investigation, we observed a reasonably low, overall incidence of postoperative lower-extremity lymphedema. Nevertheless, when evaluating the potential for lymphedema in patients for whom a lymphadenectomy is indicated, specific risk factors should be considered in an effort to attenuate the development of this morbid condition.

A Randomized Controlled Pilot Study Comparing the Impact of Aprepitant and Fosaprepitant on Chemotherapy Induced Nausea and Vomiting in Patients Treated for Gynecologic Cancer.

OBJECTIVE: The purpose of this pilot study was to compare the response rates and daily living activities of patients with newly diagnosed gynecologic cancer treated with fosaprepitant or aprepitant in the management of chemotherapy-induced nausea and vomiting. METHODS AND MATERIALS: Eligible participants were randomized to either intravenous fosaprepitant (150 mg, day 1) or oral aprepitant (125 mg on day 1 and 80 mg on days 2-3) before undergoing weekly paclitaxel (80 mg/2)(2) and monthly carboplatin (AUC 6)-based chemotherapy. In addition, standard premedications (eg, ranitidine, dexamethasone, and diphenhydramine) were administered intravenously on day 1. Response evaluation and impact on daily life were measured throughout the acute phase (0-24 hours), delayed period (days 2-4), and overall phase (0-120 hours) of the patients' initial chemotherapy cycle via the Functional Living Index-Emesis. RESULTS: In the current investigation, 20 gynecologic cancer subjects were treated with either fosaprepitant (n = 10) or aprepitant (n = 10) before their first chemotherapy cycle. We observed 7 overall complete responses (70%, no emetic episodes or rescue medications) in the aprepitant group and 6 (60%) in the fosaprepitant cohort (P = 0.660). In addition, both treatment groups reported similarly, favorable rates of daily living activities throughout the acute (P = 0.626) and delayed (P = 0.648) phases of cycle 1 chemotherapy. CONCLUSIONS: The findings from the current analysis suggest that intravenous fosaprepitant and oral aprepitant confer beneficial antiemetic prevention. Moreover, the 2 medications theoretically afford a favorable impact on daily living, thereby potentially facilitating the completion of a patient's clinically prescribed chemotherapy regimen.

Survival rate comparisons amongst cervical cancer patients treated with an open, robotic-assisted or laparoscopic radical hysterectomy: A five year experience.

BACKGROUND: The purpose of this retrospective study was to assess the 5-year survival outcomes of cervical cancer patients who underwent an, open radical hysterectomy (ORH), robotic-assisted radical hysterectomy (RRH) or laparoscopic radical hysterectomy (LRH) for the treatment of their disease. METHOD: We conducted a review of all cervical cancer patients who were managed with an ORH, RRH or LRH. RESULT: Forty-nine patients were treated with LRH, 58 were managed via RRH and 39 patients underwent an ORH. The LRH (1.78 h) patients had a significantly shorter operative duration than the RRH (2.88 h) and ORH (2.39 h) subjects (p < 0.001). Blood loss was the highest in the ORH (475 cc) group (RRH = 207 cc and LRH = 312 cc) (P < 0.001). Moreover, the ORH (5.04 days) patients had a significantly longer hospital stay than the LRH (2.95 days) and RRH (2.50 day) subjects (P < 0.001). Kaplan-Meier survival analysis revealed a progression free survival (PFS) rate of 84.6% for the ORH group, 89.8% for the LRH group and 89.7% for the RRH patients (P = 0.271) at 60 months; overall survival was 92.3% for the ORH group, 95.9% for the LRH group and 96.6% for the RRH patients (P = 0.80). CONCLUSION: The results from this study suggest that, irrespective of operative approach, patients who underwent a radical hysterectomy for early stage cervical cancer attained similar 5-year disease free and overall survival outcomes.

Dramatically reduced incidence of vaginal cuff dehiscence in gynecologic patients undergoing endoscopic closure with barbed sutures: A retrospective cohort study.

INTRODUCTION: This retrospective study documented the rate of vaginal cuff dehiscence (VCD) in a large series of gynecologic patients who were treated with an endoscopic (robotic-assisted or laparoscopic) hysterectomy that incorporated either delayed absorbable monofilament barbed or vicryl running sutures. METHOD: We sought to discern any prognostic associations between operative variables (e.g., closure type (barbed or vicryl sutures), endoscopic approach (robotic-assisted or laparoscopic), and energy source (Harmonic Ace Shears or monopolar/bipolar electro-surgery)) and the risk for VCD via patient chart review. Statistical evaluation was comprised of univariate analyses and multiple regression. RESULTS: We identified 1876 subjects; there were 14 cases (0% with barbed suture and 0.99% with vicryl suture) of VCD (an overall incidence of 0.75%), nearly all of which were associated with a robotic-assisted hysterectomy involving vicryl sutures (p = 0.034). However, the type of endoscopic surgery (P = 0.11) and energy source (P = 0.28) were not significant prognostic factors. The VCD patients' exhibited a median duration of 47 days (range, 14-116) until the development of their condition. CONCLUSION: Vaginal cuff separation subsequent to laparoscopic closure is a rare occurrence. While our incidence of VCD was low and comparable to other reported rates in the literature, we did not observe any cases of VCD following laparoscopic hysterectomy performed with barbed suture closure.

A comparison of open surgery, robotic-assisted surgery and conventional laparoscopic surgery in the treatment of morbidly obese endometrial cancer patients.

BACKGROUND AND OBJECTIVES: The intent of this retrospective study was to assess the operative outcomes of morbidly obese endometrial cancer patients who were treated with either open surgery (OS) or a minimally invasive procedure. METHODS: Morbidly obese (body mass index [BMI] > 40 kg/m(2)) patients with endometrial cancer who underwent OS, robotic-assisted laparoscopic surgery (RS), or conventional laparoscopic surgery (LS) were eligible. We sought to discern any outcome differences with regard to operative time, perioperative complications, and hospital stay. RESULTS: Sixteen patients were treated with LS (BMI = 47.9 kg/m(2)), 13 were managed via RS (BMI = 51.2 kg/m(2)), and 24 underwent OS (BMI = 53.7 kg/m(2)). The OS (1.35 hours) patients had a significantly shorter operative duration than the LS (1.82 hours) and RS (2.78 hours) patients (P < .001); blood loss was greater in the OS (250 mL) group in comparison with the RS (100 mL) and LS (175 mL) patients (P = .002). Moreover, the OS (4 days) subjects had a significantly longer hospital stay than the LS (2 days) and RS (2 days) patients (P = .002). CONCLUSION: In the present study, we ascertained that minimally invasive surgery was associated with longer operative times but lower rates of blood loss and shorter hospital stay duration compared with treatment comprising an open procedure.

Intra-abdominal temperature distribution during consolidation hyperthermic intraperitoneal chemotherapy with carboplatin in the treatment of advanced stage ovarian carcinoma.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) involves the continuous heating and circulation of chemotherapy throughout the abdominal cavity in an attempt to enhance cytotoxicity. Despite the potential of this chemotherapy procedure, there are scant anatomical temperature distribution studies reporting on this therapeutic process. PATIENTS AND METHODS: We prospectively evaluated the temperature of select anatomical (e.g. upper abdominal, mid-abdominal and supra-pubic) sites in 11 advanced stage ovarian cancer patients who were treated with consolidation HIPEC carboplatin (AUC 10). The temperature of the aforementioned anatomical regions and the inflow/outflow tubing was measured at baseline and at 15-min intervals until the procedure's completion. RESULTS: The lowest observed mean composite temperature was 41.1 °C at the supra-pubic site whereas the highest temperature was 42.6 °C, in association with the inflow/outflow tubing. During the various time intervals we also ascertained that the lowest composite temperature was 40.9 °C at baseline (i.e. time 0), whereas the highest value (41.8 °C) occurred at multiple time periods (e.g., 15, 45 and 60 min). CONCLUSION: The HIPEC temperature variation amongst the various abdominal sites and time intervals was minimal. We also discerned that uniform temperature distribution throughout the abdominal cavity was facilitated when the abdomen was both maximally distended with fluid and a high flow rate was maintained.