Effects of a green tea extract, Polyphenon E, on systemic biomarkers of growth factor signalling in women with hormone receptor-negative breast cancer.

BACKGROUND: Observational and experimental data support a potential breast cancer chemopreventive effect of green tea. METHODS: We conducted an ancillary study using archived blood/urine from a phase IB randomised, placebo-controlled dose escalation trial of an oral green tea extract, Polyphenon E (Poly E), in breast cancer patients. Using an adaptive trial design, women with stage I-III breast cancer who completed adjuvant treatment were randomised to Poly E 400 mg (n = 16), 600 mg (n = 11) and 800 mg (n = 3) twice daily or matching placebo (n = 10) for 6 months. Blood and urine collection occurred at baseline, and at 2, 4 and 6 months. Biological endpoints included growth factor [serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], lipid (serum cholesterol, triglycerides), oxidative damage and inflammatory biomarkers. RESULTS: From July 2007-August 2009, 40 women were enrolled and 34 (26 Poly E, eight placebo) were evaluable for biomarker endpoints. At 2 months, the Poly E group (all dose levels combined) compared to placebo had a significant decrease in mean serum HGF levels (-12.7% versus +6.3%, P = 0.04). This trend persisted at 4 and 6 months but was no longer statistically significant. For the Poly E group, serum VEGF decreased by 11.5% at 2 months (P = 0.02) and 13.9% at 4 months (P = 0.05) but did not differ compared to placebo. At 2 months, there was a trend toward a decrease in serum cholesterol with Poly E (P = 0.08). No significant differences were observed for other biomarkers. CONCLUSIONS: Our findings suggest potential mechanistic actions of tea polyphenols in growth factor signalling, angiogenesis and lipid metabolism.

Human papillomavirus genotype 16 vaccines for cervical cancer prophylaxis and treatment.

More than 11% of the global cancer incidence in females is due to human papillomavirus (HPV) infections, with HPV genotype 16 the most prevalent viral type to infect the cervix. Vaccine strategies currently target HPV 16 genes E6 and E7, constitutively expressed in cervical cancer cells, and L1 and L2, HPV surface antigens. Recent developments in HPV vaccine research are reviewed. Most studies focus on vaccine models showing improved immunogenicity or dual induction of both humeral and cellular systems. Preclinical studies show that (1) L1 /E7 chimeric viral-like proteins induce both neutralizing L1 antibodies and E7-specific T cells; (2) rerouting a cytosolic tumor antigen into the endosomal/lysosomal compartment can improve the therapeutic potency of DNA vaccines; and (3) accelerated E7 protein degradation leads to enhanced antigen presentation in the context of major histocompatability complex class I. Clinical studies show that (1) HPV 16 E7 peptide vaccination can be safely delivered to patients with terminal disease; and (2) HPV-16 capsid proteins harbor at least one HLA-A*201 restricted cytotoxic T lymphocyte (CTL) epitope.

Dose intensity analysis of high-dose carboplatin in refractory ovarian carcinoma relative to age.

BACKGROUND: Cisplatin and carboplatin are essential to management of advanced-stage epithelial ovarian carcinoma. No published data exist regarding carboplatin dose intensity importance in ovarian cancer, nor are there data for the effect of age on the ability to deliver dose-intensive carboplatin. METHODS: Retrospective dose intensity analyses were performed for 93 patients with advanced-stage refractory ovarian carcinoma, who received single-agent, high-dose carboplatin chemotherapy (800 mg/m2/35 days of 160 mg/m2/week). These patients had been treated on one of three high-dose carboplatin studies conducted in the Medicine Branch of the National Cancer Institute during the 1980s. Eligibility criteria required age greater than or equal to 18 years, good end organ function, and good performance status. RESULTS: Patients 60 years of age or older comprised 33% of the cohort and patients 70 years of age or older comprised 8% of the cohort. Administered dose intensity of carboplatin did not differ among age groups. Patients of age < or = 39 years received a dose intensity of 136 +/- 28 mg/m2/week, those of age 40-59 years received 129 +/- 33, those of age > or = 60 years received 134 +/- 24, and those of age > or = 70 years received 129 +/- 19. Further, the administered carboplatin dose intensity did not differ among clinical response groups. Dose intensity in complete responders was 138 +/- 18 mg/m2/week; in partial responders, 121 +/- 29; and in nonresponders, 134 +/- 30. The age distribution of responders matched the age distribution of the cohort. CONCLUSIONS: These data demonstrate that elderly patients with good end organ function and good performance status tolerate the same level of dose-intensive platinum therapy as younger patients. Age alone should not be a determinant for carboplatin dose modification in the treatment of ovarian carcinoma.

Nephrotoxicity and hydration management for cisplatin, carboplatin, and ormaplatin.

Renal toxicity is a prominent component of the toxicity profile of platinum-based chemotherapy. Kidney damage, once dose limiting for cisplatin, occurs in some patients who receive carboplatin and may occur with the third-generation platinum analog ormaplatin. Herein, we review what is known about the pathophysiology of therapy-induced renal toxicity for each of these agents and what is known about appropriate maneuvers to circumvent this toxicity. For cisplatin, hydration is always indicated and mannitol may be useful in selected settings. Furosemide is probably not generally useful. For carboplatin, hydration is important for patients with impaired renal function and for patients receiving high doses of drug (> or = 800 mg/m2). For ormplatin, renal toxicity appears not be prominent when hydration is administered in a fashion similar to cisplatin hydration. Detailed suggestions regarding the protection of kidney function when using these compounds are presented.

SEER data, corpus uteri cancer: treatment trends versus survival for FIGO stage II, 1988-1994.

OBJECTIVE: 1998 Surveillance, Epidemiology, and End Results (SEER) data estimate an 83.1% 5-year survival rate for corpus uteri adenocarcinoma FIGO stage II. The SEER data were evaluated to determine whether primary treatment differences using simple hysterectomy or radical hysterectomy, with or without radiation, altered disease survival. MATERIALS AND METHODS: SEER incidence data for FIGO II uterine corpus cancer of adenocarcinoma histology from 1988 to 1994 were stratified by hysterectomy type (simple versus radical) and whether radiation was given. Survival rates were calculated using a relative survival method and are expressed as percentages. Statistical analysis was done using a Z test. RESULTS: The 5-year cumulative survival rate for patients with stage II uterine corpus adenocarcinoma who received surgery alone as primary therapy was 84.36% with simple hysterectomy and 92.96% with radical hysterectomy (P<0.05). Survival for patients who received combination radiation and surgery as primary therapy was 82.77% with simple hysterectomy and 88.02% with radical hysterectomy (P<0.05). Pelvic and para-aortic nodes were negative. There was no significant survival difference for radiation versus no radiation in either surgical group. CONCLUSION: Radical hysterectomy is associated with better survival when compared to simple hysterectomy for FIGO II corpus uteri adenocarcinoma.

Taxol and platinum chemotherapy in the treatment of pancreatic and jejunal carcinoma.

Pancreatic cancer and jejunal cancer are aggressive diseases with grim prognoses. The long term survival of pancreatic carcinoma is still one of the worst of all cancers. Ninety-five percent of the patients die of their disease within 5 years [Wagener et al: Ann Oncol 5(Suppl 3): S87-S90, 1994]. Eighty-five percent of patients with jejunal carcinoma die of their disease within 5 years [Lioe, Biggart: J Clin Pathol 43:533-536, 1990]. To date, there are disappointingly few effective cytotoxic agents in the treatment of these cancers. We present a case of advanced-stage pancreatic carcinoma and a case of advanced stage jejunal carcinoma, each showing marked response to Taxol and platinum chemotherapy.

Cisplatin, adriamycin, etoposide, megestrol acetate versus melphalan, 5-fluorouracil, medroxyprogesterone acetate in the treatment of endometrial carcinoma.

Fifty consecutive patients with documented advanced or recurrent endometrial carcinoma from 1978 through 1985 were prospectively treated with melphalan, 5-fluorouracil, medroxyprogesterone acetate (MFP) as first-line chemotherapy. From 1987 through 1993, 50 consecutive patients with documented advanced or recurrent endometrial carcinoma were prospectively treated with cisplatin, Adriamycin, etoposide, megestrol acetate (PAV-M) as first-line chemotherapy. Response rates for MFP versus PAV-M, 2- and 5-year survival, median survival, 2- and 5-year progression-free survival, and median progression-free survival were not statistically different. However, there was a significant improvement favoring PAV-M in 2-year (45 versus 14%), 5-year (30 versus 5%), and median survival (22.3 versus 8.7 months) (P = 0.008) compared to MFP in patients with primary advanced endometrial adenocarcinoma. Moreover, there was a significant improvement in 2- and 5-year and median survival (55 and 15% and 26.7 months) for PAV-M compared to MFP (7 and 0% and 7.3 months) (P = 0.002) for the more aggressive other adenocarcinomas (adenosquamous, clear cell, papillary serous, undifferentiated) compared to the more common endometrioid adenocarcinoma. The current data suggest that cisplatin- and adriamycin-based chemotherapy results in some long-term survival benefit for patients with primary advanced endometrial adenocarcinoma and the more aggressive nonendometrioid adenocarcinoma histologies.

Tubal ligation and the risk of ovarian carcinoma.

To assess the relationship of tubal ligation and risk of ovarian carcinoma, we conducted a case-control, retrospective analysis of 300 ovarian carcinoma cases and 606 nonmalignant disease controls, seen between 1982 and 1988 at Roswell Park Cancer Institute, Buffalo, New York. Women who had a tubal ligation had reduced risk for the development of ovarian cancer. This relative risk was 0.52, with a 95% confidence interval 0.31 to 0.85 (p = 0.0076). Controls were matched by age. Multivariate analysis adjusted for socioeconomic level, marital status, parity, age at first pregnancy, menarche age, menopause age, irregular menses, breast-feeding duration, body habitus, and oral contraceptive use. Suggested explanations for this observation are offered.

PIP: Previous studies have revealed a significant inverse association between tubal ligation and ovarian cancer. To confirm this finding, a retrospective review was conducted of 300 ovarian carcinoma cases and 606 age-matched nonmalignant disease controls seen during 1982-88 at Roswell Park Cancer Institute (Buffalo, New York). Both cases and controls had completed a 16-page epidemiologic questionnaire on reproductive history and sociodemographic factors. Tubal ligation was reported by 27 women with ovarian cancer and 94 controls, resulting in a relative risk of 0.52 (95% confidence interval, 0.31-0.85) (p = 0.0076) for the development of ovarian cancer following tubal ligation. This risk was not altered by adjustment for socioeconomic status, marital status, nulligravidity, age at first pregnancy, age at menarche, age at menopause, irregular menses, breast feeding duration, body habitus, age, or oral contraceptive use. There was a significant trend (p = 0.0192) according to age at tubal ligation; the relative risks of developing ovarian cancer were 0.20, 0.44, 0.63, and 0.89 for women who had a tubal ligation at ages 24 years or less, 25-34 years, 35-44 years, and 45-58 years, respectively. It has been hypothesized that tubal ligation decreases ovarian cancer risk by preventing environmental carcinogens from reaching the ovaries; alternatively, tubal ligation may alter ovarian circulation and hormonal function.

An animal study of different treatments to prevent postoperative pelvic adhesions.

A study was designed to test various high-molecular-weight solutions in the prevention of postoperative intraabdominal adhesions. The bicornuate rat uterus was used as the surgical model, and 80 mature white female rats underwent surgical injury of the right uterine horn. The rats were randomly divided into 5 groups: groups A, B, and C received 5 ml intraperitoneally of chondroitin sulfate, sodium carboxymethylcellulose, and 32% dextran 70, respectively; group D was treated with microsurgical repair; and group E, the control, received no therapy. The animals were killed postoperatively, and the adhesions were scored. Significantly better results in adhesion prevention were demonstrated in the sodium carboxymethylcellulose group vs. the other groups, except in group A where the difference was not significant.