Concurrent chemoradiation for locally advanced carcinoma of the cervix: where are we in 2006?
Explore the source record for details and available documents.
Combined Modality Therapy↗
Biomedical subjects
P G Rose
Publications and source records attributed to P G Rose.
Chemoradiotherapy for cervical cancer.
Cervical cancer remains a major health problem worldwide, despite advances in screening. For patients with locally advanced stage disease, failure to obtain local-regional control usually results in death. In an effort to improve local-regional tumour control, neoadjuvant and concurrent chemoradiation has been tested. Recently, five randomised trials performed by the Gynecologic Oncology Group (GOG), Radiation Therapy Oncology Group (RTOG) and the SouthWest Oncology Group (SWOG) studying cisplatin-based chemoradiation have demonstrated a significant survival advantage. Three of the trials compared cisplatin-based concurrent chemotherapy and radiation to radiation alone and two trials compared cisplatin-based concurrent chemotherapy and radiation to radiation with hydroxyurea. In all of the trials, cisplatin-based chemotherapy administered concurrently with radiation therapy was more effective at reducing the risk of death by 30-50%. Acute toxicities, principally neutropenia and gastrointestinal, were more common with chemoradiation, but were transient and the rates of late complications (complications that persisted or occurred for more than 60 days after the treatment) were similar. Based on the results of these five randomised trials, the National Cancer Institute (NCI) released a Clinical Announcement stating that cisplatin-based chemotherapy, as used in these trials (i.e. concurrently with radiation therapy), as the new standard of therapy for cervical cancer.
Antineoplastic Combined Chemotherapy Protocols↗
Re: annual report to the nation on the status of cancer (1973 through 1998), featuring cancer with recent increasing trends.
Explore the source record for details and available documents.
Humans↗
Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: a gynecologic oncology group study.
PURPOSE: A phase II study was conducted to determine the efficacy of paclitaxel and valspodar (PSC 833) in patients with advanced epithelial ovarian cancer. Valspodar, a nonimmunosuppressive cyclosporine D analogue that reverses P-glycoprotein-mediated multidrug resistance, in combination with paclitaxel might be active in paclitaxel-resistant and refractory ovarian cancer. PATIENTS AND METHODS: Patients received valspodar 5 mg/kg orally qid x 12 doses. Paclitaxel (70 mg/m(2) intravenously for 3 hours) was administered on day 2, 2 hours after the fifth or sixth dose of valspodar. This treatment was repeated every 21 days. One blood sample was collected before the sixth dose of valspodar for the first three cycles to evaluate valspodar trough concentration. Tumor tissue was obtained from patients for immunohistochemical staining of P-glycoprotein. RESULTS: Of 60 patients entered, 58 were assessable for response. There were five partial responses (8.6%; 90% confidence interval [CI], 3.8 to 20.0; median duration of response, 5.0 months [range, 1.9 to 10.5 months]). Median progression-free survival was 1.5 months (90% CI, 1.4 to 2.4). Grade 3 or 4 toxicities observed were neutropenia, anemia, nausea and vomiting, peripheral neuropathy, and cerebellar ataxia. The trough concentrations of valspodar were > or = 1,000 ng/mL in all but two of 40 patients in the first cycle. Immunohistochemical staining for P-glycoprotein was positive for one of two responding patients. CONCLUSION: Valspodar in combination with paclitaxel has limited activity in patients with paclitaxel-resistant ovarian carcinoma. An international randomized clinical trial of paclitaxel and carboplatin with or without valspodar as first-line therapy in advanced ovarian cancer is underway.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group Study.
PURPOSE: A phase II trial of paclitaxel was initiated in advanced nonsquamous carcinoma of the cervix to determine its activity in patients who had failed standard chemotherapy. PATIENTS AND METHODS: Eligible patients had at least one measurable lesion. The starting dose of paclitaxel was 170 mg/m(2) (135 mg/m(2) for patients with prior pelvic radiation) given as a 24-hour continuous intravenous infusion with courses repeated every 3 weeks. Dose escalation to 200 mg/m(2) and de-escalation to 110 mg/m(2) were allowed based on adverse effects. RESULTS: In this trial, 42 assessable patients were initially entered onto the study, and 13 responses were seen; four patients had a complete response, and nine patients had a partial response. The overall response rate was 31%. The primary and dose-limiting toxicity was neutropenia. CONCLUSION: The response rate to paclitaxel exceeds the rates reported using other single agents in nonsquamous carcinoma of the cervix.
Adult↗
Type II radical hysterectomy: evaluating its role in cervical cancer.
Explore the source record for details and available documents.
Female↗
Chemotherapy in the treatment of locally advanced cervical cancer during pregnancy.
Explore the source record for details and available documents.
Combined Modality Therapy↗
Positive emission tomography for evaluating a complete clinical response in patients with ovarian or peritoneal carcinoma: correlation with second-look laparotomy.
OBJECTIVE: Positive emission tomography (PET) provides a novel means of imaging malignancies. The following study was undertaken to evaluate the predictive value of PET in determining a pathologic complete response in patients with advanced ovarian or peritoneal carcinoma who had a complete clinical response following primary chemotherapy. METHODS: Twenty-two patients with advanced-stage ovarian (N = 17) or peritoneal (N = 5) carcinoma who had achieved complete clinical and radiologic remission and normal CA-125 level after six cycles of chemotherapy and who had consented to a second look laparotomy procedure were studied. All patients received platinum based therapy and all but one patient, treated elsewhere, received paclitaxel in combination with platinum. Following IV administration of 20 mCi [(18)F]fluorodeoxyglucose (FDG), the entire abdomen and pelvis were scanned. Various technical modifications including bladder activity dilution, intravenous hydration with diuretic therapy, and mechanical bowel preparations, were used to reduce background activity. Second-look laparotomy findings were classified as negative, macroscopically positive if a biopsy of a suspicious area was histologically positive, or microscopically positive if only a nonsuspicious area was histologically positive. The effect of patient preparation prior to PET imaging was evaluated. RESULTS: Persistent disease was found in 13 of the 22 patients (59%). Only one of nine sites with macroscopic and none of four with microscopic disease were accurately predicted. The sensitivity was only 10% and the specificity 42%. Intravenous hydration, diuretic therapy, and bowel preparation did not improve the results. CONCLUSIONS: These results suggest that despite technical modifications the sensitivity of PET before second-look laparotomy for small-volume persistent disease is low.
Adenocarcinoma, Mucinous↗
Liposomal doxorubicin in ovarian, peritoneal, and tubal carcinoma: a retrospective comparative study of single-agent dosages.
PURPOSE: The aim of this study was to evaluate the relative activity and tolerance of liposomal doxorubicin in recurrent ovarian, peritoneal, and tubal carcinoma at an initial dose of 40 or 50 mg/m(2) every 4 weeks. METHODS: A retrospective single-institution study was performed on patients who received liposomal doxorubicin from 1/97 to 12/00. Demographic data, liposomal doxorubicin dose, dose reductions, response, and progression-free and overall survival were recorded. RESULTS: Seventy-eight patients, 38 treated at 40 mg/m(2) and 40 treated at 50 mg/m(2), were identified. There was no difference with respect to patient age, performance status, percentage of patients who were platinum resistant or paclitaxel resistant, or tumor bulk. The response rate in this highly resistant population was 13.5 and 7.7% for liposomal doxorubicin at 40 and 50 mg/m(2) every 4 weeks, respectively. Stable disease was observed in 49 and 51% of patients treated with liposomal doxorubicin at a dose of 40 and 50 mg/m(2) every 4 weeks, respectively. The progression-free survival for patients with responding and stable disease was similar. Dose reductions were required in 27.5% of patients treated at 50 mg/m(2) versus no patients treated at 40 mg/m(2) (P < 0.001). Treatment delays due to toxicity were required in 32.5% of patients treated at 50 mg/m(2) versus 16% of patients treated at 40 mg/m(2) (P = 0.14). CONCLUSION: Liposomal doxorubicin at a dose of 40 mg/m(2) appears to be as active as liposomal doxorubicin at a dose of 50 mg/m(2) in ovarian, peritoneal, and tubal carcinoma and is better tolerated based on the frequency of dose reductions and treatment delays.
Adult↗
Improved therapeutic index of lower dose topotecan chemotherapy in recurrent ovarian cancer.
OBJECTIVE: Topotecan (1.5 mg/m(2)) administered daily for 5 consecutive days of a 21-day cycle is an established chemotherapeutic regimen in recurrent ovarian cancer. However, noncumulative myelosuppression has limited its use by many clinicians. We sought to determine whether a lower dose of topotecan could provide comparable tumor activity and higher tolerability in pretreated ovarian cancer patients. METHODS: A retrospective chart review was conducted on recurrent ovarian, peritoneal, or fallopian tube cancer patients with measurable disease or elevated cancer antigen 125 levels (evaluable disease). Patients were treated with topotecan (1.0 mg/m(2)) given by 30-min intravenous infusion for 5 consecutive days every 21 days until disease progression or unacceptable toxicity. RESULTS: Treatment records from 37 women who had been treated with a median of 3 courses (range, 1 to 17) of lower dose topotecan were evaluated; all were evaluable for tolerability and 36 were evaluable for response. Patients had received a median of 3 (range, 1 to 6) previous treatments. The overall response rate was 22% (8/36); the response rates for patients with evaluable disease and measurable disease were 35.7 (5/14) and 13.6% (3/22), respectively. An additional 8 patients (22%) achieved stable disease. Grade 4 neutropenia, thrombocytopenia, and anemia occurred in 48.6, 5.4, and 5.4% of patients, respectively. Granulocyte colony-stimulating factor support was used in 37% of patients, including 5 who experienced febrile neutropenia. CONCLUSION: Topotecan at 1.0 mg/m(2) x 5 days every 21 days is active in platinum- and paclitaxel-resistant ovarian cancer, with significant improvements in hematologic toxicity. In heavily pretreated patients-topotecan can be safely given at reduced doses without apparent loss of efficacy.
Adult↗
Radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation and subsequent pregnancy in the treatment of early invasive cervical cancer.
BACKGROUND: Recently, pregnancies in patients after radical vaginal trachelectomy and laparoscopic pelvic lymphadenectomy have been reported. Radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation has been previously described; however, subsequent outcome and pregnancy has not. METHODS: Three patients with cervical carcinoma, 1 with stage IA1 with lymph-vascular space invasion and 2 with stage IA2, were treated with radical abdominal trachelectomy and pelvic lymphadenectomy with uterine conservation. RESULTS: All patients underwent the planned procedure with no significant intraoperative or postoperative complications. All patients had return to normal menstrual function. One patient had a successful pregnancy delivered at 39 weeks by cesarean section and is now subsequently pregnant with a second pregnancy. CONCLUSION: Radical abdominal trachelectomy is a technically feasible operation that uses operative techniques familiar to the American-trained gynecologic oncologist and results in wider parametrial resection than radical vaginal trachelectomy. In young patients desiring to retain fertility, successful pregnancies after radical abdominal trachelectomy are possible. Intraoperative and postoperative complications are likely to be lower with an abdominal versus a vaginal approach. Long-term survival of patients treated with radical trachelectomy for early invasive cervical cancer are yet to be determined.
Adenocarcinoma↗
Locally advanced cervical cancer.
Cervical cancer is a tremendous health problem as the third most frequent cancer affecting women. Locally advanced disease, which exceeds that successfully treated with surgery, is a common presentation of unscreened women. The use of concurrent chemotherapy and radiation therapy has resulted in a significant increase in patient survival. Our understanding of cervical tumor biology has the potential for further improvements.
Combined Modality Therapy↗
Germline BRCA2 mutation in a patient with fallopian tube carcinoma: a case report.
OBJECTIVES: Fallopian tube carcinoma is similar to ovarian and peritoneal carcinoma with respect to histology, response to chemotherapy, and prognosis. BRCA germline mutations have been commonly reported in ovarian and peritoneal carcinoma but rarely in other gynecologic cancers. METHODS: A patient with fallopian tube carcinoma and a family history of ovarian carcinoma underwent genetic counseling and BRCA testing as did her daughter. RESULTS: The patient and her daughter were found to have a germline BRCA2 mutation. CONCLUSION: Like a family history of ovarian or peritoneal carcinoma, the occurrence of fallopian tube cancer should alert the clinician to the possibility of an abnormality in the breast cancer susceptibility 1 or 2 genes.
BRCA2 Protein↗
Analysis of the cost effectiveness of concurrent cisplatin-based chemoradiation in cervical cancer: implications from five randomized trials.
PURPOSE: Five recent phase III trials provide strong evidence that a new alternative therapy, cisplatin-based chemoradiation, is more effective than standard therapy using radiation alone in the treatment of advanced cervical cancer. We conducted a pharmacoeconomic analysis to determine whether the alternative cisplatin-based chemoradiation is cost effective as compared with standard therapy using radiation alone. METHODS: Using an economic model, we applied costs to resource utilization data derived from the cisplatin-based chemoradiation arms of these five randomized trials. We examined the cisplatin-based chemoradiation benefits in terms of increased median survival time. Incremental costs were divided by difference in survival to determine the cost per patient benefited. Incremental cost per year of life gained (IC/YLG) was calculated based on both published and estimated survival figures. RESULTS: Cost per year of life gained for cisplatin-based chemoradiation regimens varied from $2384 to $28,770 based on published survival and from $308 to $3712 based on estimated survival. Variations in regimen cost were largely dependent on treatment setting. Administration costs per patient for cisplatin and fluorouracil in the inpatient setting were $8839 compared with $3590 in the outpatient setting. CONCLUSION: The increased median survival cost per year of life gained with cisplatin-based chemoradiation (inpatient and outpatient settings) adds a substantial benefit at an acceptable cost compared with radiation therapy alone.
Adult↗
A phase II and pharmacokinetic study of weekly 72-h topotecan infusion in patients with platinum-resistant and paclitaxel-resistant ovarian carcinoma.
BACKGROUND: As suggested by preclinical trials, prolonged administration of topotecan, a reversible inhibitor of topoisomerase-I, may have a therapeutic advantage. Following a phase I trial of weekly 72-h topotecan infusion, we performed a phase II trial utilizing this schedule in ovarian carcinoma. METHODS: Eligibility included platinum-/paclitaxel-resistant ovarian carcinoma, measurable disease, and adequate hematologic, renal, and hepatic function. A dose of 2.0 mg/m(2) of topotecan was administered as a 72-h infusion weekly via an ambulatory pump. Plasma topotecan concentrations were determined prior to and at the completion of each weekly course. RESULTS: Twenty-four patients were entered and 23 patients were evaluable for toxicity and response. Two hundred eighteen weekly courses of therapy were administered (median 7 weeks, range 4-46 weeks). Toxicity was mild with grade 3 leukopenia, neutropenia, and anemia occurring in 13, 13, and 17% of patients, respectively. Two of 23 patients (9.1%) (CI 1-28%) had partial responses of 2 and 3 months' duration and 6 had stable disease. Steady state plasma topotecan lactone concentrations were a median of 1.2 ng/ml (range 0.4-8.00 ng/ml) following the first week of infusion. Steady state topotecan lactone concentrations after the first week of infusion were highest in 2 patients with partial responses. Mean steady state plasma topotecan lactone concentrations after the first week of infusion were 4.6, 2.0, and 1.3 ng/ml for partial response, stable disease, and progressive disease, respectively. An analysis of variance of steady state plasma topotecan concentrations after the first week of infusion over all administered cycles demonstrated a significant difference in steady state plasma topotecan lactone concentrations between patients with partial response and stable disease and between partial response and no response (significant at the 0.05 level after adjustment for multiple comparisons). Controlling for cycle number, steady state topotecan lactone concentrations are significantly greater for patients with responding or stable disease than those with progressive disease (P = 0.0003) and have a lower bound of > or = 1.9 ng/ml (95% confidence level). CONCLUSION: Steady state topotecan lactone concentrations are associated with responding or stable disease in platinum- and paclitaxel-resistant ovarian cancer. Steady state topotecan concentrations could potentially be utilized to modify tumor exposure and response.
Adult↗
A phase II trial of anastrozole in advanced recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study.
BACKGROUND: Some endometrial cancers are hormonally dependent. A principal source of circulating estrogen is conversion of adrenal androstenedione by aromatase. Anastrozole (Arimidex) is an oral nonsteroidal aromatase inhibitor which is active in recurrent breast cancer. This Phase II study was undertaken to evaluate anastrozole in recurrent endometrial carcinoma. METHODS: Patients with advanced or recurrent endometrial cancer not curable with either surgery or radiation therapy and with measurable disease, a GOG (Zubrod) performance status of < or = 2, no more than one prior hormonal therapy regimen, and no prior chemotherapy were eligible. Anastrozole was administered at a dose of 1 mg/day orally for at least 28 days. RESULTS: Twenty-three patients were entered on this trial. On central pathology review, 9 of them had grade 2 and 14 had grade 3 tumors. One to 24 courses (median: 1) of therapy were administered. Two partial responses were noted (9%; 90% confidence interval 3 to 23%). Two additional patients had short-term stable disease. With the exception of 1 case of venous thrombosis, the toxicity profile was mild. Median durations of progression-free survival and overall survival are 1 and 6 months, respectively. CONCLUSIONS: Anastrozole has minimal activity in an unselected population of patients with recurrent endometrial cancer.
Administration, Oral↗
Exacerbation of endometriosis as a result of premenopausal tamoxifen exposure.
A 41-year-old woman with a history of endometriosis had breast carcinoma diagnosed and treated with tamoxifen. A pelvic mass was subsequently diagnosed and observed on serial ultrasonographic examinations to increase in size. At surgery extensive endometriosis was found. Exacerbation of endometriosis by tamoxifen may become more common as tamoxifen is used more frequently to reduce the risk of breast cancer among premenopausal women.
Adult↗
Acute encephalopathy due to aluminum toxicity successfully treated by combined intravenous deferoxamine and hemodialysis.
Acute aluminum intoxication is uncommon in clinical practice but can be fatal. This limited experience is reflected in the paucity of data assessing a viable approach to the treatment of these patients. In this report, the authors describe the clinical course and successful, pharmacokinetic-based deferoxamine-hemodialysis treatment regimen of a patient with severe aluminum encephalopathy following alum bladder irrigation. The combined use of deferoxamine and appropriately timed hemodialysis appears to be a very reasonable means of treating patients with severe acute aluminum intoxication.
Acute Disease↗