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A Manetta

Publications and source records attributed to A Manetta.

At least 37 records · Page 2Linked to original sources

Retrospective review of gynecologic oncology patients with therapy-induced neutropenic fever.

We reviewed the course and outcome of gynecologic oncology patients with neutropenic fever (NF), and identified low-risk patients who might be candidates for outpatient management. Charts from patients with the discharge diagnosis of NF from 1990 to 1994 were reviewed for variables related to the febrile neutropenic episode. Outcome was evaluated in terms of the duration of neutropenia, length of hospital stay, NF treatment result, incidence of positive blood cultures, dose reduction in the subsequent course of chemotherapy, and death. Statistical associations between variables and outcome parameters were examined by the Student t test and chi 2 or Fisher's exact tests as indicated. Multivariate analysis by logistic regression was done to determine independent significance of variables. Forty-five episodes of NF were identified involving 40 patients. The median duration of neutropenia following the diagnosis of NF was 2.5 days. The source of fever was unexplained by exam or cultures in 25/45 (56%) episodes. There were two (4%) deaths. In 16/45 episodes, patients had been treated with at least one prior regimen of chemotherapy (median, eight courses). Episodes of NF in patients receiving second-line chemotherapy were associated with a prolonged time of neutropenia (> 3 days, P = 0.058); however, this did not translate into increased hospital stay, treatment failure, or death. Thirteen of 45 (29%) NF episodes developed in patients while already hospitalized for medical or surgical conditions. In this group, cultures were positive in 64% of cases. The remaining 32 NF episodes developed in patients while at home. Patients who developed outpatient NF (ONF) had positive cultures in 23% of cases (P = 0.08) and had a median hospital stay of 4 days. No patient with ONF who remained hemodynamically stable during the first 12 hr of admission suffered serious morbidity. In a multivariate analysis, only bacteremia approached statistical significance in predicting a longer hospital stay (P = 0.07), and no variable studied was predictive of prolonged NF in the ONF group. Our retrospective analysis indicates that patients with ONF who remain stable during the initial 12 hr of hospitalization might safely be discharged home with appropriate antibiotics. Prospective study of outpatient management of NF is required to confirm these findings.

Adult↗

Radiation-induced CA 125 production by mesothelial cells.

CA 125 levels are often falsely elevated in disease-free endometrial cancer patients who have undergone abdominal radiation therapy. Because peritoneal irritation or mediators of inflammation can induce CA 125 production in mesothelium, the possibility that irradiated cultured mesothelial cells secrete CA 125 was investigated. Seven mesothelial cell isolates, an ovarian cell line which does not secrete CA 125, normal mammary epithelium, and normal fibroblasts were exposed to 500 cGy of 6-MV photon irradiation. Irradiated mesothelial cells showed little or no growth, while untreated cells increased in number. Twenty-four-hour CA 125 production was measured in the tissue culture medium on Day 4, and daily for one mesothelial cell isolate. Radiation stimulated CA 125 secretion in mesothelial cells up to 32 times over nonirradiated controls. The time course study showed that CA 125 levels increased rapidly in irradiated cells by Day 3 and remained elevated for the next 3 days. Increased immunoreactivity for p53 in irradiated mesothelial cells confirmed that a protein known to be radiation-inducible could be produced by the same conditions. Normal fibroblasts, mammary epithelium, and the ovarian cell line did not produce CA 125 in either the presence or absence of radiation. Thus, irradiated mesothelial cells are a potential source of serum CA 125 in patients who have received abdominal irradiation.

Adult↗

A study of biomarkers in cervical carcinoma and clinical correlation of the novel biomarker MN.

The MN protein is a newly described biomarker found to be overexpressed in most cervical carcinomas. This study was an effort to evaluate the prognostic importance of tumor MN expression, HPV status, and the presence of other biomarkers in cervical cancers. Tumor DNA and protein for study were extracted from archived frozen tissue. Tumor tissues and controls were evaluated by Western blot analysis for MN, intestinal alkaline phosphatase (IAP), c-myc, and p53 protein overexpression. Immunohistochemistry was performed for MN quantification and the study of expression patterns in histologic subtypes of cervical cancer. HPV data were obtained by PCR amplification of extracted DNA using consensus and type-specific primers. Clinical data were obtained from the patients' records and from the cancer registry. Clinical and molecular data were correlated by chi2, Fisher's exact test, and logistic regression. The results demonstrate that IAP is not overexpressed in clinical specimens of cervical carcinoma, although in somatic cell hybrid experiments, overexpression of IAP correlates with the malignant state. None of 47 tumors, including those which were HPV negative, overexpressed p53. c-myc protein overexpression occurred in 11 of 52 tumors, most of which contained HPV 16, but this was not significantly different from the tumors as a whole. There was no apparent association between MN protein expression and the overexpression of c-myc protein. MN was overexpressed in all cancers and quantitatively varied with the histologic subtype. Specifically, lower expression of MN correlated with adenosquamous and less-differentiated histology (P < 0.01 for grade 3 tumors). Low expression of MN protein also correlated with HPV negativity (P < 0.05). In stage IB and IIA cancers, low expression of MN was associated with deeper cervical stromal invasion (P < 0.03). Further, low expression of MN correlated with lymph node metastases in small (<3.5 cm) IB and IIA cervical cancers (P < 0.04). These data suggest that MN is emerging as a potentially important new biomarker for cervical carcinoma. The overexpression commonly seen in cervical cancer is possibly associated with loss of a critical tumor suppressor gene located on chromosome 11. Low expression of MN antigen appears to correlate with several adverse prognostic features and further prospective study is warranted.

Adult↗

Development and characterization of an interleukin-2-transduced human ovarian carcinoma tumor vaccine not expressing major histocompatibility complex molecules.

OBJECTIVE: We initiated studies to develop cytokine-secreting human ovarian carcinoma cells for the purpose of using these cells as vaccines for the treatment of advanced epithelial ovarian cancer. STUDY DESIGN: A human ovarian carcinoma cell line (UCI-107) was genetically engineered to secrete the cytokine interleukin-2 by retroviral-mediated gene transduction. RESULTS: One clone, termed UCI-107A IL-2 AS, constitutively secreted high levels of interleukin-2 (i.e., 2000 to 2300 pg/ml/10(5) cells per 48 hours) for > 55 passages and 8 months of study. Unlike parental- and vector-transduced cells, UCI-107A IL-2 AS cells were aneuploid and failed to express major histocompatibility complex class I and HER2/neu surface antigens. UCI-107A IL-2 AS cells were highly resistant to killing by gamma irradiation and continued to produce high levels of interleukin-2 even after irradiation with 10,000 cGy. Balb/C nude mice injected intraperitoneally with UCI 107-A IL-2 AS cells survived significantly longer than control animals, with 25% of the animals totally rejecting their tumors. UCI-107A IL-2 AS was totally resistant to killing by fresh allogeneic peripheral blood lymphocytes in four hour chromium 51 release assays but induced high levels of killing in 72-hour long-term cytotoxic assays. CONCLUSION: The potential use of these interleukin-2-secreting ovarian carcinoma cells as vaccines for women with advance ovarian cancer will be discussed.

Adenocarcinoma, Papillary↗

Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer.

PURPOSE: Serious cumulative toxicity is a well-recognized consequence of chemotherapy. Amifostine, an organic thiophosphate, has demonstrated the ability to protect selectively a broad range of normal, but not neoplastic, tissues from the cytotoxic effects of chemotherapy and radiotherapy. This study was designed to determine if amifostine could reduce the serious toxicities associated with cyclophosphamide and cisplatin (CP), without reducing antitumor efficacy in patients with ovarian cancer. PATIENTS AND METHODS: Two hundred forty-two patients with advanced ovarian cancer were randomized to receive six cycles of cyclophosphamide (1,000 mg/m2) and cisplatin (100 mg/m2) with or without amifostine (910 mg/m2) every 3 weeks for six cycles. The occurrence of hematologic, renal, neurologic, and ototoxicity was evaluated. Antitumor efficacy was assessed by pathologic tumor response and survival. RESULTS: Pretreatment with amifostine before each cycle of chemotherapy resulted in a reduction of cumulative toxicities. Hematologic toxicity consisted of grade 4 neutropenia associated with fever and/or infection that required antibiotic therapy (P = .005), days in hospital (P = .019), and days on antibiotics (P = .031). Platinum-specific toxicities consisted of protracted serum creatinine elevations (P = 0.004), > or = 40% reduction from baseline in creatinine clearance (P = .001), and severity of neurologic toxicity (P = .029). Twenty-four percent of CP patients compared with 9% of amifostine plus CP patients discontinued therapy because of protocol-specified toxicity (P = .002). Pathologic tumor response rates were 37% with amifostine and 28% in controls, with comparable median survival times of 31 months. Amifostine was generally well tolerated; the principal side effects were emesis and a transient decrease in blood pressure. CONCLUSION: Pretreatment with amifostine reduces the cumulative hematologic, renal, and neurologic toxicities associated with the CP regimen, with no reduction in antitumor efficacy.

Adult↗

beta-Carotene treatment of cervical intraepithelial neoplasia: a phase II study.

The use of Papanicolaou smears for cervical cancer screening has led to an increased detection of preinvasive conditions of the cervix, cervical intraepithelial neoplasia (CIN). Epidemiological studies have shown an association between low levels of dietary beta-carotene and CIN. In this Phase II study, we have explored the effect of p.o. beta-carotene administration on CIN I and II. Patients with documented CIN I or II were treated with 30 mg daily of beta-carotene for 6 months. Response rates were determined at 0, 3, 6, and 12 months with cytology, colposcopy, and/or biopsies. Levels of beta-carotene and vitamin E were determined at the same time intervals in vaginal mucosa cells and serum. Response rates were 18 of 30 (60%), 21 of 30 (70%), and 10 of 30 (33%) at 3, 6, and 12 months, respectively. Significant changes occurred in the serum beta-carotene levels over time. Median levels over 2200 mg/ml were found at 3 and 6 months versus a baseline median level of 111 (P < 0.0001). Significant increases were also noted in the beta-carotene levels of the vaginal mucosa compared to baseline (P = 0.01) and a significant correlation was noted between serum and vaginal beta-carotene levels as well (P < 0.0001). This study indicates that a large percentage of patients with CIN I and II will respond clinically to p.o. beta-carotene supplementation. There is a positive relationship between serum and tissue levels of beta-carotene which suggests that serum levels can be used for monitoring purposes. Because of these encouraging results, prospective randomized studies are ongoing comparing the efficacy of beta-carotene against an untreated control arm.

Antioxidants↗

UCI-VULV-1, a vulvar squamous carcinoma cell line.

Squamous carcinoma of the vulva (SCV) is an uncommon neoplasm of uncertain etiology. There is evidence that there are two subgroups of SCV, one associated with human papilloma virus (HPV) and a second HPV-negative group. The UCI-VULV-1 cell line, obtained from a lymph node metastasis of an SCV, grows with a population doubling time of approximately 60 hr. The saturation density is 10(5) cells/cm2. The cell line does not exhibit anchorage independence and is weakly tumorigenic. The cells range in appearance from an abundant spindle cell to a less common larger, flat cell. All of the cells are immunoreactive for high-molecular-weight keratin, but only the flat cells, which form squamous pearls in vivo, are immunoreactive for low-molecular-weight keratin. The cell line expresses epidermal growth factor (EGF), transforming growth factor-alpha, the EGF receptor, and p53 protein. Polymerase chain reaction revealed no HPV DNA within the cells. Early passage cells exhibited karyotypic heterogeneity with few similarities to previous described SCV karyotypes. The cells display sensitivity to cis-platinum in concentrations toxic to many ovarian and cervical carcinoma lines. UCI-VULV-1 may be helpful for studying the properties of the HPV-negative form of SCV.

Aged↗

Neoadjuvant chemotherapy with vincristine and cisplatin followed by radical hysterectomy and pelvic lymphadenectomy for FIGO stage IB bulky cervical cancer: a Gynecologic Oncology Group pilot study.

Thirty-five patients with bulky (designated as > or = 4 cm size) International Federation of Gynaecology and Obstetrics (FIGO) Stage IB cervical cancer were treated with cisplatin, 50 mg/m2, and vincristine, 1 mg/m2, administered intravenously at 10-day intervals for a total of three courses before planned radical hysterectomy. One patient died of unrelated cause following one course of chemotherapy and was not evaluated for response. Of the 34 evaluable patients who completed chemotherapy, a complete clinical response was noted in two patients (6%) and a partial response in 26 patients (76%). Five patients (15%) had stable disease and one patient (3%) had disease progression. All chemotherapy was completed within 4 weeks (range 17-28 days). There was no grade 4 toxicity noted. Only one case each of reversible grade 3 granulocytopenia and stomatitis and two cases of reversible grade 3 peripheral neuropathy were noted. Of the 34 patients who received chemotherapy, the only patient with disease progression received standard pelvic radiation therapy in lieu of radical surgery. A second patient with stable disease had unresectable pelvic lymph node metastases and underwent confirmatory lymph node biopsy only and received standard radiation therapy postoperatively. The remaining 32 patients underwent radical hysterectomy and pelvic lymphadenectomy from 12 to 49 days following chemotherapy. Surgery was performed without significant difficulty. Eight of these patients (25%) had pelvic node metastases and received postoperative pelvic radiation therapy. Twenty-four months following initiation of treatment, 25 (74%) were alive and presumed free of disease, 4 had died of cancer (12%), 1 was alive with recurrence (3%), and 4 patients (12%) were lost to follow-up. A prospective randomized study is needed to assess the value of this approach compared with standard management.

Adenocarcinoma↗

Characterization and development of UCI 107, a primary human ovarian carcinoma cell line.

We introduce a new epithelial ovarian carcinoma cell line (UCI 107) from a patient with papillary adenocarcinoma of the ovary who had not been previously treated. The growth characteristics, chemosensitivity, tumorgenicity, cytogenetics, antigen expression, and receptor status were examined. A standardized photometric assay was implemented to determine the response to single drug agents including doxorubicin (ADR), cisplatin (CDDP), and Taxol. Tumorgenicity was determined utilizing female athymic mice implanted either subcutaneously (sc) or intraperitoneally (ip) with 1 x 10(7) UCI 107 cells. UCI 107 cells grow rapidly in culture with lag phase of approximately 48 hr, population doubling time of 24-36 hr, and saturation density of 4.8 x 10(5) cells/cm2. The 50% inhibitory concentration values for the chemotherapeutic agents were 0.170, 0.029, and 0.330 microM for ADR, Taxol, and CDDP, respectively. Nude mice produced ip tumors within 15 days, resulting in death from carcinomatosis 40-45 days postimplantation. Subcutaneous tumor nodules (100 mm3) were observed in nude mice 12-13 days post-tumor implantation reaching a maximum tumor volume of approximately 10,000 mm3 by Day 30. The cytogenetic composite karyotype is as follows: 46, X, der (X) t (X;7) (p11;q22), inv dup (1) (q12;q32), t (6;6;11;22) (p21.3;q16;q23.3;q13.3), del (13) (q14.1). The cell line expresses progesterone receptor, increased levels of p53 protein, and cytokeratins. It does not appear to express Her-2/neu protein, estrogen receptor, nor the CA 125 tumor marker. In conclusion, UCI 107 displays unique cellular properties which make it an attractive model for the study of ovarian cancer.

Animals↗

Endometrioid adenocarcinoma of the ovary and its relationship to endometriosis.

In order to better understand the clinical presentation and biologic behavior of ovarian carcinomas arising in endometriosis, we performed a historical cohort study of all women with endometrioid adenocarcinoma of the ovary (ECO) diagnosed between 1979 and 1991 at our institutions. A review of pathology reports determined the presence or absence of coexisting endometriosis. Cancers adjacent to endometriosis on the same ovary or arising within endometriosis were labeled endometriosis-associated endometrioid adenocarcinoma (EAEA), while all others were considered typical endometrioid adenocarcinoma (TEA). Associations between tumor type and clinicopathologic variables were analyzed by chi 2 and Fisher's exact tests as indicated. Disease-free interval (DFI) and overall survival were estimated using the Kaplan-Meier method. The independent prognostic significance of clinicopathologic variables was determined by multivariate analysis using the Cox proportional hazards regression model. Of 91 ECO patients identified, 63 (69%) had TEA and 28 (31%) had EAEA. Significant differences between TEA and EAEA existed for age at diagnosis (greater than 55 years; 56 vs 32%, P = 0.039), nulliparity (19 vs 46%, P = 0.007), stage (I and II combined; 37 vs 70%, P = 0.004), and disease status at completion of primary surgery (complete tumor resection; 47 vs 70%, P = 0.04). Synchronous atypical endometrial hyperplasia or uterine carcinoma was found in 7/63 (11%) TEA versus 7/28 (25%) EAEA cases (P = 0.054). Estimated 5-year DFI by life table analysis was significantly longer in the EAEA than in the TEA cohorts (57 vs 25%, P = 0.02); however, the 5-year survival difference was not significant (59 vs 45%, P = 0.18). Multivariate analysis identified only stage as an independent prognostic factor in predicting both DFI and survival. In conclusion, women with EAEA are significantly younger, present with earlier stage disease, and have a longer disease-free survival than those with TEA. These factors may reflect a more favorable biologic behavior of ECO when arising in association with endometriosis.

Adult↗

A phase II trial of neoadjuvant chemotherapy prior to radical hysterectomy and/or radiation therapy in the management of advanced carcinoma of the uterine cervix.

OBJECTIVE: This prospective trial was designed to access the efficacy and safety of neoadjuvant chemotherapy followed by radical hysterectomy and/or radiation therapy in women with advanced carcinoma of the uterine cervix. METHODS: Thirty women, clinical stages IIb-IVa, were enrolled in this clinical trial. Initial treatment consisted of three cycles of bleomycin, cisplatin, and vincristine administered every 10 days. Depending on the extent of disease after chemotherapy, patients then either underwent radical hysterectomy with bilateral pelvic and periaortic lymphadenectomy or surgical staging. Following review of the surgical findings, tailored radiotherapy was administered. RESULTS: Only 10 women (34%) had tumor regression from neoadjuvant chemotherapy sufficient to allow radical hysterectomy prior to tailored adjuvant radiotherapy; the remainder received primary radiotherapy after surgical staging. Two-year disease-free survival was 68, 43, and 0% for women with clinical stages II, III, and IV, respectively. Four women experienced acute toxicity from chemotherapy requiring medical intervention and eight women suffered chronic toxicities requiring hospitalization and/or surgery. CONCLUSION: The neoadjuvant chemotherapy utilized in this trial was generally ineffective in converting patients from inoperable to operable, had no apparent effect on survival, and was associated with significant toxicity.

Adult↗

Use of ileocecal continent urinary reservoir in patients with previous pelvic irradiation.

OBJECTIVE: To assess the results of the use of ileocecal continent urinary reservoirs in patients with previous pelvic irradiation. METHODS: A retrospective analysis for morbidity and clinical outcome was undertaken for 37 female patients with prior therapeutic pelvic irradiation who underwent continent urinary diversion with a detubularized right colonic segment as the urinary reservoir, a plicated ileocecal valve as the continence mechanism, and a tapered distal ileum for efferent catheterization. RESULTS: Thirty-one patients had persistent or recurrent pelvic malignancies, 17 of whom had total pelvic exenteration and 14 had anterior exenteration. The remaining 6 patients had radiation-induced vesicovaginal fistulas without evidence of recurrence and underwent urinary diversion alone. Follow-up ranged from 2 to 33 months (median 11 months). Postoperative radiographic evaluation revealed no evidence of urinary extravasation. Of the 74 implanted ureters, 4 had reflux (5%), 2 developed stricture (3%), and 5 had mild to moderate hydronephrosis (7%). All patients achieved daytime continence with catheterization intervals of 3-8 hr (median 4 hr) and capacities of 200-1000 cc (median 500 cc). Nighttime continence was reported by 33 of 37 patients (89%). Reoperation was required in 3 patients (8%), 2 with stoma stenosis and 1 with difficulty in catheterization. CONCLUSIONS: The use of the ileocecal continent urinary reservoir in patients with previous pelvic irradiation achieves results comparable to those reported for nonirradiated patients, thus supporting its use in this select group of patients.

Female↗

Does perioperative blood transfusion affect survival in patients with cervical cancer treated with radical hysterectomy?

OBJECTIVE: To determine if blood transfusions during or after radical hysterectomy adversely affect survival in patients with invasive cervical carcinoma. METHODS: Two hundred eighty-three women with stage IA2-IIA cervical cancer were treated with radical hysterectomy and pelvic lymphadenectomy from 1980-1989. Thirteen were lost to follow-up, and five others received adjuvant chemotherapy. Among the remaining 265 patients, 131 were given blood transfusions during surgery or within 30 days, whereas 134 were not. The clinical and pathologic characteristics of these two groups were reviewed and analyzed statistically. RESULTS: Transfused and nontransfused patients did not differ with respect to mean age (45.0 versus 43.4 years, respectively), stage, grade, cell type, depth of invasion, or prevalence of nodal metastasis. Transfused patients more frequently received adjuvant pelvic irradiation than did nontransfused (47 versus 33%, respectively, chi 2 P < .05). After a mean follow-up of 51 months (range 13-125), 19 women (14%) in each group were diagnosed as having recurrent disease, predominantly in the pelvis. Using life-table analysis, the calculated 5-year survival was 86% for transfused and 84% for nontransfused patients, a nonsignificant difference. Disease-free survival was also similar. In the study population, grade, depth of invasion, and nodal status predicted survival. When patients were stratified according to age, cell type, stage, depth of invasion, nodal involvement, and use of adjuvant radiation, blood transfusion still did not adversely influence survival. Using the Cox proportional hazards model, only nodal status was an independent predictor of death. CONCLUSION: Perioperative blood transfusion does not impact overall survival or time to recurrence after radical hysterectomy.

Adult↗

Single-visit program for cervical cancer prevention in a high-risk population.

OBJECTIVE: To evaluate the feasibility of a single-visit cervical neoplasia screening and intervention program. METHODS: A sample of asymptomatic, nonpregnant, indigent, adult women who had not had a Papanicolaou smear for at least 2 years (N = 126) was recruited through Spanish-language media in Orange County, California. Women who volunteered underwent a free, single-visit program combining a health questionnaire, education, an immediately read Papanicolaou smear, loop electrosurgical excision of the transformation zone for those with dysplastic cytology, and an exit questionnaire gauging satisfaction and educational impact. Main outcome measures included the frequency of cervical cancer risk factors and barriers to health care, incidence of cervical neoplasia, feasibility, short-term educational impact, and acceptability of interventions. RESULTS: All 126 patients had at least one cervical cancer risk factor; 101 (80.2%) reported at least one barrier to health care. One hundred sixteen (92.1%) had a normal Papanicolaou smear, and three (2.4%) with a mildly atypical smear were referred for colposcopy. Seven (5.6%) patients had a dysplastic smear and underwent same-day loop electrosurgical excision of the transformation zone without complication, with histology revealing koilocytotic atypia (two patients), cervical intraepithelial neoplasia (CIN) I (two), CIN II (two), and CIN III (one). No case of invasive cervical carcinoma was identified. The mean time from performance of Papanicolaou smear to receipt of cytologic results was 2.2 hours, and the mean total visit time was 3.6 hours. Patients found the single-visit program to be both beneficial and satisfying. CONCLUSION: This single-visit program is feasible and may overcome barriers to the diagnosis and management of cervical neoplasia in patients at high risk.

Adult↗

Spontaneous release of interleukin-6 by primary cultures of lymphoid and tumor cell populations purified from human ovarian carcinoma.

Interleukin-6 (IL-6) is a cytokine that has been implicated as a growth factor in human ovarian carcinoma, yet the in vivo source of IL-6 in patients remains undefined. We measured IL-6 by ELISA in cell-free ascites (CFA) of 19 patients with ovarian carcinoma. IL-6 was detectable in all samples (mean level 3.3 ng/ml). To identify the cellular source of IL-6, we measured this cytokine by ELISA in 24-48 h supernatants of cultured lymphocyte-, macrophage-, and tumor cell-enriched populations purified from three solid ovarian carcinomas by centrifugal elutriation. All cell populations spontaneously released IL-6; however, tumor cells and tumor-associated macrophage released levels of IL-6 that greatly exceeded those released by tumor-associated lymphocytes. Kinetic studies revealed that IL-6 was detectable at 6 h and that levels increased in all cultures examined over a 48 h time course. These data suggest that both tumor and infiltrating host cells may be the source of the high levels of IL-6 found in carcinomatous ascites. Furthermore, although all three cell types examined may contribute to IL-6 production in patients with ovarian carcinoma, tumor cells are perhaps the most clinically significant source.

Adenocarcinoma↗

Prevention of cervical intraepithelial neoplasia and cervical cancer.

We review the current status of prevention trials in the management of cervical intraepithelial neoplasia (CIN) and cervical cancer. Two large, randomized controlled trials have shown that folic acid is inactive in reversing low to moderate grade CIN. A large randomized trial of locally applied beta-trans retinoic acid showed that the agent was effective in reversing moderate but not severe CIN. Results from a pilot trial involving 30 patients with CIN I (mild dysplasia) and CIN II (moderate dysplasia) indicate that beta-carotene can suppress CIN; a large ongoing randomized trial will answer the question more definitively.

Antioxidants↗

A phase II study of fazarabine in patients with advanced ovarian cancer. A Gynecologic Oncology Group study.

BACKGROUND: A total of 22 patients with recurrent ovarian cancer previously treated with cisplatin-containing chemotherapy were treated with Fazarabine. METHODS: The drug was administered at an initial dose of 30 mg/m2/day for 5 consecutive days. Cycles were repeated every 28 days. There were 19 evaluable patients. RESULTS: No complete or partial responders were observed in this study; 48% of patients were deemed to have stable disease. The major toxicity was hematologic, with four patients exhibiting grade 4 neutropenia. CONCLUSIONS: Fazarabine shows no useful activity as a single agent when given at this dose and schedule in the management of previously treated patients with cancer of the ovary.

Adenocarcinoma↗

A phase II study of fazarabine (NSC 281272) in patients with advanced squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study.

Promising preclinical data and reasonable toxicity in Phase I trials encouraged the Gynecologic Oncology Group to study Fazarabine (FZB) in patients with recurrent squamous cell cancer of the cervix. Twenty-three patients with histologically proven recurrent cervical cancer with measurable disease received FZB at a dosage of 30 mg/m2 per day for 5 days; cycles repeated every 28 days. In the absence of grade 3 or 4 toxicity, dose escalation was planned to a maximum dose of 40 mg/m2 per day for 5 days. All patients were evaluable for toxicity. Seven patients developed neutropenia; in two instances, it was considered life-threatening. The only other serious adverse effect was seen in one patient who developed grade 4 nephrotoxicity. Nineteen women who had failed prior chemotherapy were evaluable for response. There were no complete or partial responses; and seven had stable disease. Fazarabine exhibits no demonstrable activity in this patient population at the dose and schedule tested and further clinical trials as second-line chemotherapy are not warranted.

Adult↗