Current status of intraperitoneal therapy for ovarian cancer

Recent attention has focused on evaluating those clinical situations in which intraperitoneal drug delivery may be an appropriate treatment option for patients with ovarian cancer. When employed as a second-line strategy, approximately 20% to 30% of patients with small-volume residual disease (microscopic, largest tumor mass < or = 0.5 to 1 cm in maximum diameter) at initiation of treatment are expected to achieve a surgically documented complete response with a variety of organoplatinum-based intraperitoneal regimens. However, responses are rarely observed in such patients who have failed to demonstrate tumor sensitivity to systemically delivered organoplatinum drugs, despite the presence of small-volume residual disease. Investigators at several centers are currently exploring a possible role for regional drug delivery in the initial management of selected patients (ie, small-volume disease) with ovarian cancer. A recently reported trial of intraperitoneal taxol suggests this may be an ideal drug for regional therapy of ovarian cancer due to a major pharmacokinetic advantage associated with this route of drug delivery.     

A proposed model for the prediction of response to endocrine therapy in breast cancer from the estrogen receptor status of one site and the number of metastatic sites

A mathematical model for prediction of response to endocrine therapy of breast cancer has been developed based on a clonal concept of metastatic spread. The model includes an expression of the likelihood of response of an estrogen receptor-positive site and an expression of the concordance of receptor assays when multiple sites are assayed. Both of these are raised to a power function based on the number of sites of metastases to yield a predicted response rate. An excellent fit of the predictions of this mathematical model and response data from a series of patients receiving endocrine therapy was observed. This model provides a worthwhile insight into the biology of response to endocrine therapy. The model may be extended and refined through additional analyses.     

An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer

Total mercury concentration in the muscle of 417 fish of 12 common freshwater and four anadromous species from Bangladesh were low, varying from 2 to 430 ng/g fresh wt. Depending on Hg speciation, three types of accumulation mechanisms were defined. Type I covers the majority of species and describes a pattern widely accepted as 'normal', with increasing levels of organic (methyl) mercury with length (age), combined to a low and constant inorganic level. This accumulation pattern leads to a relative increase of the organic mercury fraction with age, eventually reaching 90-100% of organic mercury in full grown specimens. Type II is found in both planktivorous genera only and showed increasing levels of inorganic mercury combined to low and constant organic mercury levels, leading to a relative decrease in organic mercury fraction with age. This unexpected pattern was only reported in cases of some marine species where it seemed to be linked to demethylation mechanisms or regional influences on Hg levels. A third intermediate accumulation pattern with increasing concentrations of both the organic and the inorganic Hg fraction with age was found in one bottom dwelling species only. The implications of these observations for the accumulation mechanisms of mercury in fish are discussed.     

乳腺癌抗血管生成治疗:现状与前景

Tumor angiogenesis plays an important role in the growth, invasion and metastasis of breast cancer, therefore recently a very active area of breast cancer research involves the addition of antiangiogenic therapy. Numerous clinical studies for several antiangiogenic agents have recently been conducted in breast cancer patients and have shown clinically significant improvement in outcomes. This review gives a brief background to breast cancer angiogenesis, also focusing on current progress in the field of antiangiogenic therapy for breast cancer and issues regarding future therapeutic development.     

Current status of monoclonal antibodies for imaging and therapy of prostate cancer

It is clear that there is significant need for improved staging and therapy of prostate cancer. The attributes and strengths of MoAbs seem particularly well-suited to the setting of prostate cancer. Recent progress in the application of MoAbs to in vivo imaging and therapy is encouraging. Clearly, further such efforts in prostate cancer are warranted.     

Systemic therapy for breast cancer

Currently available information suggests that the optimal duration of adjuvant therapy for breast cancer patients with no involved axillary nodes is 5 years, though controversy about this recommendation persists. In postmenopausal patients, disease-free survival appears to be improved by the addition of combination chemotherapy to tamoxifen. Recently reported studies indicate that there is no benefit to dose escalation of cyclophosphamide in adjuvant therapy and that the risk of secondary leukemia may be increased. The combination of paclitaxel and doxorubicin has been reported in single-institution studies to produce high response rates but may also be cardiotoxic. Recent reports indicate that a pharmacokinetic interaction between these two drugs may cause these clinical findings. New agents that may be of utility in the management of advanced or primary breast cancer include novel hormonal agents, notably the aromatase inhibitors, and the bisphosphonates.     

Gene therapy for breast cancer

Gene therapy for breast cancer is still in the very early stages of development. Many of the molecular strategies that have been proposed are also being developed for other cancers. Their application to breast cancer, however, needs to address several issues specific to this disease such as the widespread nature of metastases, the indolent growth of the tumor cells, and the production by the tumor of immunosuppressive agents. Nonetheless, these approaches appear promising, particularly those that employ a combination of strategies. Gene therapies that affect the biology of breast cancer cells or regulate host immune mechanisms have been most successful and may be paired with existing therapies for breast cancer.     

Change in emotion-regulation strategy for women with metastatic breast cancer following supportive-expressive group therapy.

Four relatively independent emotion-regulation constructs (suppression of negative affect, restraint, repression, and emotional self-efficacy) were tested as outcomes in a randomized trial of supportive-expressive group therapy for women with metastatic breast cancer. Results indicate that report of suppression of negative affect decreased and restraint of aggressive, inconsiderate, impulsive, and irresponsible behavior increased in the treatment group as compared with controls over 1 year in the group. Groups did not differ over time on repression or emotional self-efficacy. This study provides evidence that emotion-focused therapy can help women with advanced breast cancer to become more expressive without becoming more hostile. Even though these aspects of emotion-regulation appear trait-like within the control group, significant change was observed with treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Primary endocrine therapy for advanced breast cancer: to start with tamoxifen or with medroxyprogesterone acetate?

BACKGROUND: The availability of compounds effective against metastatic disease and at the same time excellently tolerated even in long-term administration has determined the choice of tamoxifen as primary treatment for palliation in metastatic breast cancer. Other drugs or other hormonal approaches were hardly tested against tamoxifen, especially as first-line treatment. PATIENTS AND METHODS: 119 patients with metastatic breast cancer and no prior endocrine therapy were randomized to receive either tamoxifen (TAM) 20 mg/day orally (64 patients), or medroxyprogesterone acetate (MAP) 1g/day i.m. 5 days/week for 4 weeks and then 500 mg twice a week (55 patients). The subsequent endocrine therapy was also prospectively defined at study entry. RESULTS: A total of 111 events, contributing to the endpoint 'time to progression' have so far been observed: a study of similar size would have a 90% power to detect a hazard ratio of 1.85. Initial MAP was associated with a significantly higher remission rate (50% versus 30% for tamoxifen; p = 0.023) and a marginally significantly longer median time to progression (8.8 versus 5.4 months; p = 0.051). Overall survival was also longer for the MAP group (28 versus 20 months; p = 0.384). The use of MAP was associated with a significantly higher toxicity, mainly hypertension, weight gain and tremor. CONCLUSIONS: The implications of these results are that initial endocrine therapy in postmenopausal patients with metastatic disease should be MAP if the patient is willing to accept the side effects of high-dose progestins. Progestins should be tested in the adjuvant setting for postmenopausal women, especially those with no tendency to hypertension or obesity.     

Oestrogen-regulated genes in breast cancer: association of pLIV1 with response to endocrine therapy

Northern hybridization analyses of the oestrogen-inducible mRNAs pLIV1 and pS2 were compared with oestrogen receptor (ER) immunocytochemistry assessments in 40 untreated primary or early recurrent breast tumours. Significant associations were observed between pLIV1/ER (P < 0.03), pS2/ER (P < 0.001) and pLIV1/pS2 (P < 0.04) status. After disease recurrence, patients were treated with assessable courses of endocrine therapies. Positive pLIV1, pS2 and ER statuses in primary disease were consequently found to be predictive of endocrine responsiveness in the secondary lesions (P < 0.03, P < 0.02, P < 0.005 respectively). However, despite these associations, a number of pLIV1- and/or pS2-positive tumours failed to respond to therapy.     

Effects of supportive-expressive group therapy on pain in women with metastatic breast cancer.

Objective: To examine whether a group intervention including hypnosis can reduce cancer pain and trait hypnotizability would moderate these effects. Design: This randomized clinical trial examined the effects of group therapy with hypnosis (supportive-expressive group therapy) plus education compared to an education-only control condition on pain over 12 months among 124 women with metastatic breast cancer. Main Outcome Measures: Pain and suffering, frequency of pain, and degree of constant pain were assessed at baseline and 4-month intervals. Those in the treatment group also reported on their experiences using the hypnosis exercises. Results: Intention-to-treat analyses indicated that the intervention resulted in significantly less increase in the intensity of pain and suffering over time, compared to the education-only group, but had no significant effects on the frequency of pain episodes or amount of constant pain, and there was no interaction of the intervention with hypnotizability. Within the intervention group, highly hypnotizable participants, compared to those less hypnotizable, reported greater benefits from hypnosis, employed self-hypnosis more often outside of group, and used it to manage other symptoms in addition to pain. Conclusion: These results augment the growing literature supporting the use of hypnosis as an adjunctive treatment for medical patients experiencing pain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)