Phase II study of paclitaxel and vinorelbine (Pacl-Vin) in hormone-refractory metastatic prostate cancer: double tubulin targeting.

BACKGROUND: Androgen ablation is the standard treatment for advanced prostate cancer. However, most patients will eventually develop progressive hormone-refractory prostate cancer (HRPC). The aim of the Pacl-Vin study was to determine the efficacy and safety of paclitaxel in combination with vinorelbine in patients with HRPC, following from a phase I trial. METHODS: Thirty castrate patients with progressive, metastatic prostate cancer were enrolled. Patients were treated with paclitaxel 40 mg/m2, vinorelbine 20 mg/m2 intravenously on day 1 and day 8 of a 21-day cycle. RESULTS: Two patients demonstrated a partial response and seven patients had stable disease from a cohort of 10 patients with measurable disease. Of 30 patients assessable for prostate-specific antigen (PSA) response, 19 showed stable disease, which was maintained for at least 4 weeks, while six (20%) experienced>or=50% decline in PSA levels. Median overall survival was 7.3 months (interquartile range (IQR): 4.7-9.9 months). Median progression-free survival was 3.3 months (IQR: 2.5-7.0 months). Improvement in quality of life measures was noted after three cycles of therapy. Grade 3 and 4 toxicities were: neutropenia 8%, febrile neutropenia 4%, infection 2%, anaemia 3%, lethargy 1% and somnolescence 1%. One patient died as a result of neutropenic sepsis. CONCLUSION: In a poor prognostic cohort of patients paclitaxel and vinorelbine is a tolerable regimen, with a 20% PSA and objective response rate. The majority of patients achieved PSA stability. Furthermore, quality of life parameters, such as pain, were improved. However, the low level of activity of this regimen precludes its further testing.

Young Women's Accounts of Sexual Activity and Sexual/ Reproductive Health.

The accounts of sexual activity and sexual health from group discussions with young women living in a variety of ethnic communities in East London, UK, were examined. Thematic decomposition was employed to explicate a number of themes: sex as technical knowledge; sexual intercourse as intimacy; naturalizing sexual activity as part of adolescent development; constraints on being sexually active and relations with young men; and constructions of young women's sexual activity within the family. These themes are discussed in terms of the salience of various complex and sometimes contradictory meanings of sex for young women, the social and cultural contexts in which young women are sexually active and seek to negotiate 'safe sex' and the implications for sex and health education addressed to young people.

Cremophor pharmacokinetics in patients receiving 3-, 6-, and 24-hour infusions of paclitaxel.

BACKGROUND: Paclitaxel (Taxol) is a new drug with efficacy against a variety of malignant tumors. The clinical formulation of paclitaxel contains 50% Cremophor EL, a polyethoxylated castor oil vehicle (carrier) that can reverse multidrug resistance (MDR) mediated by P-glycoprotein. Three-hour intravenous infusions of paclitaxel can yield end-of-infusion plasma Cremophor concentrations of 1 microL/mL or more, which are sufficient to reverse MDR in vitro by at least 50%. Despite extensive clinical use, the pharmacokinetics of Cremophor have not been described. PURPOSE: We studied the pharmacokinetics of Cremophor in patients with ovarian cancer who were undergoing treatment with paclitaxel to determine whether plasma Cremophor concentrations achieved during and following 3-, 6-, and 24-hour drug infusions were similar to those shown to modulate MDR in vitro. METHODS: Eleven patients with previously treated (i.e., with platinum-containing chemotherapy regimens) ovarian cancer were randomly assigned to receive one 3-hour, one 6-hour, and one 24-hour infusion of paclitaxel in varied sequences during their first three cycles of treatment with this drug. Blood samples were collected both during and following the three infusion periods, and Cremophor concentrations in these samples were measured by use of a bioassay based on the ability of Cremophor in plasma samples to reverse cellular resistance to daunorubicin in vitro. RESULTS: Ten patients were treated with paclitaxel at a dose level of 175 mg/m2, and one patient was treated at a dose level of 135 mg/m2. At the 175-mg/m2 dose level, peak plasma Cremophor concentrations of 1 microL/mL or more were achieved in eight of 10 patients during both the 3-hour and the 6-hour infusions; with the 24-hour infusion, only one patient achieved a peak plasma Cremophor concentration of 1 microL/mL or more. The eight patients who achieved plasma Cremophor concentrations of 1 microL/mL during the 3-hour infusion were above this level 30 minutes into the infusion; the total time that the plasma concentration was greater than 1 microL/mL was 8.9 +/- 5.0 hours (mean +/- standard deviation; range, 4.1-15.6 hours). For the eight patients who achieved plasma Cremophor concentrations of 1 microL/mL during the 6-hour infusion, the total time that the concentration was greater than 1 microL/mL was 10.2 +/- 9.0 hours (range, 0.3-21.9 hours). The patient who received paclitaxel at a dose of 135 mg/m2 achieved a peak plasma Cremophor concentration of 1 microL/mL or more only during the 3-hour infusion. CONCLUSIONS: Paclitaxel infusions of 3 and 6 hours can result in sustained plasma Cremophor concentrations sufficient for substantial reversal of P-glycoprotein-mediated MDR in vitro. These plasma Cremophor concentrations are not achieved during 24-hour infusions of paclitaxel.

The ideas and experiences of pregnancy and childbirth of Asian and non-Asian women in east London.

This study examined differences between the ideas and experiences of pregnancy and childbirth of Asian and non-Asian women giving birth in East London, and sources of variability in Asian women's accounts. In line with the findings of previous research, Asian women's ideas about diet in pregnancy, the gender of their children and postnatal care (e.g. the need for rest and recovery, and restrictions on their activities) were influenced by cultural beliefs and practices. However, in other ways Asian women demonstrated a strong commitment to Western maternity care. In contrast to some other studies Asian women wanted their husbands or partners present at delivery, indicating the extent to which traditional ideas are being modified. Qualitative analysis of Asian women's fuller accounts indicated that women subscribed to traditional practice as well as Western maternity care. Acculturation or familiarity with Western ideas about maternity care was associated with variability in Asian women's ideas and experiences, in line with previous research. However, in spite of frequent assumptions about its significance, religion was not associated with variability in Asian women's ideas and experiences. Parity, however, was a major variable, for Asian and for non-Asian women, suggesting that the first birth has different significance for parents than subsequent births. The implications for the provision of maternity care are discussed, especially the need to go beyond stereotypical views based on women's ethnicity or religion to consider the beliefs and preferences of women as individuals and their personal circumstances.

Postnatal care: the attitudes and experiences of Asian women in east London.

Thirty-two Asian women living in East London were interviewed about their experiences of childbirth. A significant part of their accounts concerned their experiences in the postnatal wards. They reported fewer difficulties with infant feeding than their non-Asian counterparts in other studies, but there were indications of similar tensions between mothers and staff about how much responsibility mothers should take for their baby's care. Asian women raised several additional issues. Some centred on communication difficulties for Asian women who did not speak fluent English. Others point to their different ideologies around the care of the mother and baby and the nature of early mother-infant relations. Asian women viewed the opportunity to rest and recover postnatally as more central to their postnatal care than they considered hospitals did. Women had less to say and seemed less familiar with the discourse on bonding, and were less preoccupied with the establishment of close mother-infant relationship. The implications for ideas about 'normal' maternal behaviour and the quality of care are discussed.

Pregnancy and antenatal care: the attitudes and experiences of Asian women.

Asian women living in the East End of London were interviewed in English or in their own language to assess their attitudes to and experiences of pregnancy and antenatal care and to consider some factors which may influence their experiences, especially their fluency in English. In some respects Asian women's experiences were similar to those of non-Asian women reported in other studies, e.g. similar levels of nausea and lack of tie-up between nausea and negative reactions to pregnancy. However there were also some differences, e.g. Asian women expressed greater concern about the sex of the child and about eating 'cool' foods to counterbalance the hot state of pregnancy. Asian women were good patients: they attended antenatal clinics, read the leaflets provided and about half attended antenatal classes, although some were keener than others to seek information about pregnancy and childbirth and only a quarter bought books or watched videos. Less than half of the women were living in extended families and receiving support from in-laws in the traditional way. Those living in nuclear families received support from friends, neighbours and especially husbands. There were considerable individual differences in women's reactions and experiences. Women who spoke little or no English were less knowledgeable and had lived for a shorter time in the UK than women who were fluent in English. Leaflets in languages women can read and link workers at clinics helped some women.

PIP: Interviewers spoke with 32 Indian or Pakistani women living in the London Borough of Newham in England to compare their experiences and expectations of maternity services with those of non-Asian UK women in other studies and to consider factors linked with variability and to examine factors associated with variability. Their pregnancy experiences often resembled those of UK women including sizable variations in the progression of pregnancy, in their reactions and means of handling pregnancy, and in their support networks. Yet some differences existed which tended to involve cultural attitudes and ideas about pregnancy and their roles. For instance, some women were embarrassed to be in public while pregnant and others ate cool foods to neutralize the hot state of pregnancy. Many women were obsessed with the sex of the infant, especially those of at least parity 2. All the women attended prenatal clinics and only 12.5% missed any prenatal care appointments. 40.6% tended to go to their appointments on their own and women who knew none or little English went alone as often as did those who were fluent in English. Pamphlets provided the leading source of information (93.75%). Other important sources included reading and buying books or watching TV programs and videos (40%). 46% attended prenatal classes. Women fluent in English were more likely to attend than women who knew none or little English, but their husbands tended to go in their place. 59.4% lived in a nuclear family and 40.6% lived in an extended family which consisted of in-laws. A few women lived with their husbands and their own parents. Support tended to come from friends and neighbors (53.1%), husbands (40.6%), and female relatives (40.6%). 18.75% did not receive any support at all. Women whose English was limited or nonexistent tended to have lived longer in England than those fluent in English and had lower knowledge levels (0 vs. 69%).

Current maternal attitudes to infant feeding methods.

Mothers' feeding practices and their attitudes to breast and bottle feeding were investigated. Sixty-four per cent started to breast feed and 35% continued past 2 months, a continuation rate which is higher than previously reported. Also higher than previously reported was the proportion of working class women breast feeding. This may reflect a current trend. Most women decided on their infant feeding technique early in pregnancy, and 80% followed that decision. For those who changed their minds about feeding practice postnatally, and for those who were initially undecided, the hospital was influential. Analysis of women's pleasurable and less restricting than they had anticipated. The results are discussed in relation to attempts to encourage breast feeding.