Fertility Status Does Not Facilitate Women’s Judgment of Male Sexual Orientation

Archives of Sexual Behavior - Previous research has demonstrated that women can correctly distinguish between gay and heterosexual men’s faces significantly better than chance. This ability...     

Population pharmacokinetics in phase I drug development: a phase I study of PK1 in patients with solid tumours

Doxorubicin pharmacokinetics were determined in 33 patients with solid tumours who received intravenous doses of 20–320 mg m⁻² HPMA copolymer bound doxorubicin (PK1) in a phase I study. Since assay constraints limited the data at lower doses, conventional analysis was not feasible and a ‘population approach’ was used. Bound concentrations were best described by a biexponential model and further analyses revealed a small influence of dose or weight on V1 but no identifiable effects of age, body surface area, renal or hepatic function. The final model was: clearance (Q) 0.194 l h⁻¹; central compartment volume (V1) 4.48 × (1+0.00074 × dose (mg)) l; peripheral compartment volume (V2) 7.94 l; intercompartmental clearance 0.685 l h⁻¹. Distribution and elimination half-lives had median estimates of 2.7 h and 49 h respectively. Free doxorubicin was present at most sampling times with concentrations around 1000 times lower than bound doxorubicin values. Data were best described using a biexponential model and the following parameters were estimated: apparent clearance 180 l h⁻¹; apparent V1 (l) 1450 × (1+0.0013 × dose (mg)), apparent V2 (l) 21 300 × (1–0.0013 × dose (mg)) × (1+2.95 × height (m)) and apparent Q 6950 l h⁻¹. Distribution and elimination half-lives were 0.13 h and 85 h respectively. © 1999 Cancer Research Campaign     

SCOTROC 2B: feasibility of carboplatin followed by docetaxel or docetaxel-irinotecan as first-line therapy for ovarian cancer

The feasibility of combination irinotecan, carboplatin and docetaxel chemotherapy as first-line treatment for advanced epithelial ovarian carcinoma was assessed. One hundred patients were randomised to receive four 3-weekly cycles of carboplatin (area under the curve (AUC) 7) followed by four 3-weekly cycles of docetaxel 100 mg m(-2) (arm A, n=51) or docetaxel 60 mg m(-2) with irinotecan 200 mg m(-2) (arm B, n=49). Neither arm met the formal feasibility criterion of an eight-cycle treatment completion rate that was statistically greater than 60% (arm A 71% (90% confidence interval (CI) 58-81%; P=0.079; arm B 67% (90% CI 55-78%; P=0.184)). Median-dose intensities were >85% of planned dose for all agents. In arms A and B, 15.6 and 12.2% of patients, respectively, withdrew owing to treatment-related toxicity. Grade 3-4 sensory neurotoxicity was more common in arm A (1.9 vs 0%) and grade 3-4 diarrhoea was more common in arm B (0.6 vs 3.5%). Of patients with radiologically evaluable disease at baseline, 50 and 48% responded to therapy in arms A and B, respectively; at median 17.1 months' follow-up, median progression-free survival was 17.1 and 15.9 months, respectively. Although both arms just failed to meet the formal statistical feasibility criteria, the observed completion rates of around 70% were reasonable. The addition of irinotecan to first-line carboplatin and docetaxel chemotherapy was generally well tolerated although associated with increased gastrointestinal toxicity. Further exploratory studies of topoisomerase-I inhibitors in this setting may be warranted.     

New directions in testicular cancer; molecular determinants of oncogenesis and treatment success

Metastatic testicular cancer is highly curable with conventional cytotoxic drugs. This is in contrast to most other metastatic solid tumours which can only be palliated with chemotherapy achieving only a modest impact on overall survival. If we could understand at the molecular level why chemotherapy is so effective in the treatment of testicular cancer, we may be better able to move other forms of metastatic cancer into the curable bracket. Most cytotoxic drugs appear to induce cell death by activating intracellular apoptotic mechanisms. Thus, the ability of a cancer to activate and execute such mechanisms in response to treatment is paramount in determining the effectiveness of chemotherapy. The basic study of cancer molecular biology is providing some insight into the proteins involved in this process and the ability to apply this information to actual human tumours is essential to rationalise clinical treatment failures at a molecular level. Testicular cancer provides an excellent model system in this analysis. Whereas there are large numbers of patients that are cured by chemotherapy, there are some whose cancers become resistant to treatment. An understanding of testicular cancer molecular biology may allow the identification of the genes regulating such a crucial behavioural switch. It may then be possible to manipulate specific signalling pathways to overcome drug resistance. This review focuses on recent developments in our understanding of the molecular biology of testicular cancer. A number of key players have been implicated including p53, pRb, cyclin D2, p INK proteins, c-kit and the bcl-2 family of proteins. The exact manner by which cellular transformation occurs has still not been established, but it is clear that many of the above proteins also have important roles in normal spermatogenesis. This is a developmental phase when the generation of genetic diversity is at a premium, but when selective apoptotic mechanisms are paramount. We discuss why this may be relevant to the behaviour of germ cell tumours and address possible reasons why they can become resistant to conventional therapy.     

Docetaxel and cisplatin in combination as first-line chemotherapy for advanced epithelial ovarian cancer. Scottish Gynaecological Cancer Trials Group.

PURPOSE: A prospective, nonrandomized, multicenter, open feasibility study of cisplatin and docetaxel as first-line chemotherapy in International Federation of Gynecology and Obstetrics (FIGO) stage IC-IV epithelial ovarian cancer was conducted. The primary end point was the incidence of severe fluid retention that necessitated treatment withdrawal. PATIENTS AND METHODS: Cisplatin and docetaxel were administered every 3 weeks for six planned cycles, with a 5-day prophylactic dexamethasone regimen (8 mg two times per day). One hundred patients (median age, 53 years; range, 24 to 71 years) received a total of 512 cycles of chemotherapy in two cohorts: cohort 1, 49 patients, 258 cycles (cisplatin 75 mg/m(2) and docetaxel 75 mg/m(2)); cohort 2, 51 patients, 254 cycles (cisplatin 75 mg/m(2) and docetaxel 85 mg/m(2)). RESULTS: No patients were taken off study because of fluid retention. Sixty-six patients completed six cycles of protocol therapy; 16 stopped early because of toxicity (neurotoxicity in six patients, nephrotoxicity in three, neutropenia in two, and hypersensitivity, diarrhea and vomiting, skin rash, clinical deterioration, and patient's wishes in one patient each). Grade 3/4 neutropenia was observed in more than 75% of patients and seemed to be cumulative. Patients in cohort 2 had significantly more severe neutropenia and lethargy than those in cohort 1. In addition, there were five treatment-related deaths in cohort 2 (three neutropenia and two upper gastrointestinal hemorrhage). Neurotoxicity (mainly sensory, > grade 1) was observed in 23 patients. The overall clinical response rate was 69% (complete response, 38%; partial response, 31%); CA-125 response rate was 73%. Median progression-free survival for the group was 12 months. CONCLUSION: Cisplatin and docetaxel can be administered at doses of 75 mg/m(2) and 75 mg/m(2), respectively, every 3 weeks, and the utility of this regimen is not limited by fluid retention. However, 33 of 100 patients were unable to complete the planned six cycles, which may explain, in part, the poor overall progression-free survival. Increasing the docetaxel dose to 85 mg/m(2) adds unacceptable hematologic toxicity and potential risks to the patient.     

Male–Female and Female–Female Mounting in Japanese Macaques: A Comparative Study of Posture and Movement

Mounting is generally considered to be a male-typical behavior. Female Japanese macaques, in certain populations, are unusual, in that they routinely mount other females. In this study, we examined to what extent female Japanese macaques mount same-sex partners in a male-typical manner. We compared the mount postures males and females adopt and their rate of pelvic thrusting. In addition, we employed a modified form of Laban Movement Analysis (LMA) to compare patterns of pelvic movement during mounts. LMA is a universal language for movement that describes quantitative features of movement, such as changes in the relation of the body segments, as well as qualitative features, such as the style of movements. Our results indicate that female Japanese macaques do not mount in a male-typical manner. Females exhibited a much greater variety of mount postures than did males. Some of the most common types of mount postures employed by females were never exhibited by males. Females performed fewer pelvic thrusts per mount than males, but they executed more pelvic movements per mount, as well as, greater variety and complexity of movement. In addition, the qualitative style of pelvic mounting that females employed differed, in general, from that of males. We argue that these sex differences in mounting can be explained by the fact that both sexes sought sexual reward via genital stimulation during mounting, but they did so in different ways owing to the constraints imposed by their genital architecture. This study raises the larger question as to what constitutes a male-typical or female-typical behavior.     

A phase Ib trial of docetaxel, carboplatin and erlotinib in ovarian, fallopian tube and primary peritoneal cancers

The safety and maximum tolerated dose (MTD) of erlotinib with docetaxel/carboplatin were assessed in patients with ovarian cancer. Chemonaive patients received intravenous docetaxel (75 mg m(-2)) and carboplatin (area under the curve 5) on day 1 of a 3-week cycle, and oral erlotinib at 50 (cohort 1), 100 (cohort 2a) or 75 mg day(-1) (cohort 2b) for up to six cycles. Dose-limiting toxicities were determined in cycle 1. Forty-five patients (median age 59 years) received treatment. Dose-limiting toxicities occurred in 1/5/5 patients (cohorts 1/2a/2b). The MTD of erlotinib in this regimen was determined to be 75 mg day(-1) (cohort 2b; the erlotinib dose was escalated to 100 mg day(-1) in 11 out of 19 patients from cycle 2 onwards). Neutropaenia was the predominant grade 3/4 haematological toxicity (85/100/95% respectively). Common non-haematological toxicities were diarrhoea, fatigue, nausea and rash. There were five complete and seven partial responses in 23 evaluable patients (52% response rate). Docetaxel/carboplatin had no measurable effect on erlotinib pharmacokinetics. In subsequent single-agent maintenance, erlotinib was given at 100-150 mg day(-1), with manageable toxicity, until tumour progression. Further investigation of erlotinib in epithelial ovarian carcinoma may be warranted, particularly as maintenance therapy.     

A dose-finding study of carboplatin-epirubicin-docetaxel in advanced epithelial ovarian cancer

The docetaxel-carboplatin combination is active and well tolerated in patients with epithelial ovarian cancer. We added epirubicin to this combination to investigate additional benefits of anthracyclines in epithelial ovarian cancer. Twenty-one patients, FIGO Ic-IV, performance status 0-1, were treated in four dose cohorts. Docetaxel was fixed at 75 mg m(-2), carboplatin doses were AUC 4-5 and epirubicin doses were 50-60 mg m(-2). Drugs were given on day 1, every 3 weeks, except in cohort 3, where epirubicin was given on day 8. Dexamethasone was given prophylactically. One dose-limiting toxicity occurred in cohorts 1, 2 and 4, two occurred in cohort 3. Complicated neutropenia occurred in two patients in cohorts 1 and 2 and one patient in cohorts 3 and 4. Two patients experienced grade III diarrhoea or stomatitis in cohort 1 and two in cohort 3. There were no treatment-related deaths. Grade II sensory neuropathy occurred in one patient. No cardiac toxicity or significant oedema was observed. The overall response rate was 36%, and 62% were CA125 responders. The predefined maximum tolerated dose was exceeded in cohort 3. The cohort 4 dose level (epirubicin 50 mg m(-2), carboplatin AUC 4, docetaxel 75 mg m(-2)), warrants further study.     

Long-Term Effects of Cancer Survivorship on the Employment of Older Workers

Objective. To estimate the long-term effects of cancer survivorship on the employment of older workers.
Data Sources. Primary data for 504 subjects who were 55–65 in 2002 and were working when diagnosed with cancer in 1997–1999, and secondary data for a comparison group of 3,903 similarly aged workers in the Health and Retirement Study (HRS) in 2002.
Study Design. Three employment outcomes (working, working full time, usual hours per week) were compared between the two groups. Both Probit/Tobit regressions and propensity score matching were used to adjust for potentially confounding differences between groups. Sociodemographic characteristics, baseline employment characteristics, and the presence of other health conditions were included as covariates.
Data Collection Methods. Four telephone interviews were conducted annually with cancer survivors identified from tumor registries at four large hospitals in Pennsylvania and Maryland. Many of the questions were taken from the HRS to facilitate comparisons.
Principal Findings. Cancer survivors of both genders worked an average of 3–5 hours less per week than HRS controls. For females, we found significant effects of survivorship on the probability of working, the probability of working full-time, and hours. For males, survivorship affected the probability of full-time employment and hours without significantly reducing the probability of working. For both genders, these effects were primarily attributable to new cancers. There were no significant effects on the employment of cancer-free survivors.
Conclusions. Survivors with recurrences or second primary tumors may particularly benefit from employment support services and workplace accommodation. Reassuringly, any long-term effects on the employment of cancer-free survivors are fairly small.