Stage IVB Cervical Cancer Research Articles

Outcomes and toxicities for the treatment of stage IVB cervical cancer

The prognosis of stage IVB cervical cancer is generally poor. In the current study, treatment outcomes were evaluated in patients with International Federation of Gynecologic Oncology stage IVB cervical cancer treated with radiotherapy and chemotherapy for progression-free survival (PFS) and treated-related toxicities. The medical records of the patients with stage IVB cervical cancer who were treated at the National Cancer Center, South Korea were reviewed retrospectively. From February 2002 to February 2010, 45 patients were diagnosed with FIGO stage IVB cervical cancer. Survival and toxicities were compared between the 13 patients with concomitant chemoradiotherapy (CCRT) with weekly cisplatin versus 20 patients with CCRT with 5-fluorouracil/cisplatin. Initial treatment included weekly cisplatin-CCRT, 5-fluorouracil/cisplatin-CCRT, neoadjuvant chemotherapy, and radiotherapy with subsequent combination chemotherapy in 13, 20, 4, and 5 patients, respectively. Overall survival (OS) and PFS were 26.2 and 6.7 months, respectively. There was no statistical difference in OS (p = 0.47) and PFS (p = 0.64) between the weekly cisplatin-CCRT and 5-fluorouracil/cisplatin-CCRT groups; however, the incidence of anemia >grade 3 as an acute toxicity was higher in the 5-fluorouracil/cisplatin-CCRT chemotherapy regimen group than the weekly cisplatin-CCRT group (p = 0.03). Acute toxicity >grade 2 showed a tendency to be higher in the 5-fluorouracil/cisplatin-CCRT group. Based on multivariate analysis, poor performance status was the only independent prognostic factor of OS (p = 0.03, 9.77; 95% CI 1.3-73.3) and PFS (p = 0.04, 9.58; 95% CI 1.14-81.26). CCRT using combination chemotherapeutic agents may not have survival advantage over single agent cisplatin-based CCRT. Further improvement in treatment is needed to increase survival outcomes and to decrease treatment-related toxicities in patients with stage IVB cervical cancer.

Phase II study of S-1, an oral fluoropyrimidine, in patients with advanced or recurrent cervical cancer

BackgroundS-1 is an oral fluoropyrimidine. This phase II study was designed to evaluate the efficacy and safety of S-1 in patients with advanced or recurrent uterine cervical cancer. Patients and methodsS-1 35 mg/m2 was given twice daily for 28 days repeated every 6 weeks. Eligible patients were women aged 20–74 years, who had Eastern Cooperative Oncology Group performance status of zero or one, who had stage IVB or recurrent uterine cervical cancer, and who had received no more than one platinum-containing chemotherapy regimen for stage IVB or recurrent disease. The primary end point was overall response rate (ORR) determined by RECIST. ResultsA total of 37 patients were enrolled in the trial and 36 were eligible. The median number of cycles administered was 4. The confirmed ORR was 30.6% (95% confidence interval 15.5% to 45.6%). The response rate for patients who had received platinum-based treatment including chemoradiotherapy was 31.8% (7 of 22). After a median follow-up duration of 25 months, the median time to progression and the median survival time were 5.2 and 15.4 months, respectively. The most frequent grade 3 or 4 adverse events were anemia (16%), anorexia (16%), and diarrhea (22%). ConclusionsThis phase II study of S-1 in cervical cancer suggests a promising response rate and a contribution toward prolonging survival, with modest toxic effects. Phase III studies of S-1 in patients with advanced or recurrent cervical cancer are thus warranted.

Outcomes and toxicities for the treatment of stage IVB cervical cancer.

e15586 Background: The prognosis of stage IVB cervical cancer is generally poor. In the current study, treatment outcomes were evaluated in patients with International Federation of Gynecologic Onc...

Topotecan for the treatment of recurrent and stage IVB carcinoma of the cervix

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of topotecan in combination with cisplatin for the treatment of recurrent and stage IVB carcinoma of the cervix, in accordance with the licensed indication, based upon the evidence submission from the manufacturer to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcomes measured were overall survival, progression-free survival, response rates, adverse effects of treatment, health-related quality of life (HRQoL) and quality-adjusted life-years (QALYs) gained. The manufacturer stated that topotecan plus cisplatin is the only combination regimen to date to have demonstrated a statistically significant survival advantage compared to cisplatin monotherapy in the licensed population. The clinical evidence came from three clinical trials comparing topotecan plus cisplatin with cisplatin monotherapy (GOG-0179), topotecan plus cisplatin with paclitaxel plus cisplatin (GOG-0169), and four cisplatin-based combination therapies: topotecan plus cisplatin, paclitaxel plus cisplatin, gemcitabine plus cisplatin, and vinorelbine plus cisplatin (GOG-0204). Results from GOG-0179 showed greater median overall survival with topotecan plus cisplatin than with cisplatin monotherapy: 9.4 months versus 6.5 months. Similar results were also reported for median progression-free survival. Response rates also showed an advantage with topotecan plus cisplatin compared with cisplatin monotherapy. The response rates in patients receiving cisplatin monotherapy were very low, but the potential reasons for this were not discussed in the manufacturer’s submission. Patients receiving topotecan plus cisplatin experienced a greater number of adverse events and the ERG was concerned with some of the assumptions related to HRQoL. In the base-case direct comparison, the incremental cost-effectiveness ratio (ICER) of topotecan plus cisplatin versus cisplatin monotherapy was £17,974 per QALY in the main licensed population, £10,928 per QALY in the cisplatin-naive population (including stage IVB patients) and £32,463 per QALY in sustained cisplatin-free interval patients. In response to the point for clarification raised by the ERG, the manufacturer submitted a revised indirect comparison incorporating HRQoL and a longer time horizon. Where the hazard ratio derived from GOG-0169 was employed, paclitaxel plus cisplatin was dominated by topotecan plus cisplatin, but, where the hazard ratio from GOG-0204 was adopted, paclitaxel plus cisplatin was found to have an ICER of £13,260 per QALY versus topotecan plus cisplatin. At present there is a paucity of evidence available on the clinical effects of topotecan plus cisplatin and the effects of palliative treatment in general for women with advanced and recurrent carcinoma of the cervix. Further trials, or the implementation of registries, are required to establish the efficacy and safety of topotecan plus cisplatin. The guidance issued by NICE in September 2009 as a result of the STA states that topotecan in combination with cisplatin is recommended as a treatment option for women with recurrent or stage IVB cervical cancer, only if they have not previously received cisplatin. Women who have previously received cisplatin and are currently being treated with topotecan in combination with cisplatin for the treatment of cervical cancer should have the option to continue therapy until they and their clinicians consider it appropriate to stop.

Topotecan for the treatment of recurrent and stage IVB carcinoma of the cervix

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of topotecan in combination with cisplatin for the treatment of recurrent and stage IVB carcinoma of the cervix, in accordance with the licensed indication, based upon the evidence submission from the manufacturer to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcomes measured were overall survival, progression-free survival, response rates, adverse effects of treatment, health-related quality of life (HRQoL) and quality-adjusted life-years (QALYs) gained. The manufacturer stated that topotecan plus cisplatin is the only combination regimen to date to have demonstrated a statistically significant survival advantage compared to cisplatin monotherapy in the licensed population. The clinical evidence came from three clinical trials comparing topotecan plus cisplatin with cisplatin monotherapy (GOG-0179), topotecan plus cisplatin with paclitaxel plus cisplatin (GOG-0169), and four cisplatin-based combination therapies: topotecan plus cisplatin, paclitaxel plus cisplatin, gemcitabine plus cisplatin, and vinorelbine plus cisplatin (GOG-0204). Results from GOG-0179 showed greater median overall survival with topotecan plus cisplatin than with cisplatin monotherapy: 9.4 months versus 6.5 months. Similar results were also reported for median progression-free survival. Response rates also showed an advantage with topotecan plus cisplatin compared with cisplatin monotherapy. The response rates in patients receiving cisplatin monotherapy were very low, but the potential reasons for this were not discussed in the manufacturer's submission. Patients receiving topotecan plus cisplatin experienced a greater number of adverse events and the ERG was concerned with some of the assumptions related to HRQoL. In the base-case direct comparison, the incremental cost-effectiveness ratio (ICER) of topotecan plus cisplatin versus cisplatin monotherapy was 17,974 pounds per QALY in the main licensed population, 10,928 pounds per QALY in the cisplatin-naive population (including stage IVB patients) and 32,463 pounds per QALY in sustained cisplatin-free interval patients. In response to the point for clarification raised by the ERG, the manufacturer submitted a revised indirect comparison incorporating HRQoL and a longer time horizon. Where the hazard ratio derived from GOG-0169 was employed, paclitaxel plus cisplatin was dominated by topotecan plus cisplatin, but, where the hazard ratio from GOG-0204 was adopted, paclitaxel plus cisplatin was found to have an ICER of 13,260 pounds per QALY versus topotecan plus cisplatin. At present there is a paucity of evidence available on the clinical effects of topotecan plus cisplatin and the effects of palliative treatment in general for women with advanced and recurrent carcinoma of the cervix. Further trials, or the implementation of registries, are required to establish the efficacy and safety of topotecan plus cisplatin. The guidance issued by NICE on 28 October 2009 as a result of the STA states that topotecan in combination with cisplatin is recommended as a treatment option for women with recurrent or stage IVB cervical cancer, only if they have not previously received cisplatin. Women who have previously received cisplatin and are currently being treated with topotecan in combination with cisplatin for the treatment of cervical cancer should have the option to continue therapy until they and their clinicians consider it appropriate to stop.

Carboplatin and paclitaxel as an initial treatment in patients with stage IVb cervical cancer: a report of 7 cases and a review of the literature

The aim of this study is to evaluate the efficacy of carboplatin-paclitaxel (TC) as an initial treatment in patients with the International Federation of Gynecology and Obstetrics (FIGO) stage IVb cervical cancer. We retrospectively reviewed seven patients with stage IVb cervical cancer who have been primarily treated with TC. The activity and the toxicity were evaluated. Response rate was the main endpoint. Overall, the treatment of TC was well tolerated. The overall response rate was 71.4% (2 complete response, 3 partial response). Although grade 3-4 hematologic toxicities were observed in 3 out of 7 patients (42.8%), no patients experienced grade 3-4 non-hematologic toxicities. When we combined our present results with the previous reports, the overall response rate of TC is 63.6%. TC is active and well tolerated in patients FIGO stage IVb cervical cancer. This combination may be considered as an initial treatment regimen in this patient population.

Outcomes of advanced and recurrent cervical cancer treated with cisplatin and generic topotecan: retrospective analysis in a tertiary care hospital in Thailand

Retrospective evaluation of the outcome of stage IVB, recurrent or persistent cervical cancer treated with cisplatin and generic topotecan (CT) in a tertiary care hospital in Thailand. The medical records of patients treated with CT regimen at Chiang Mai University Hospital between January 2005 and December 2007 were reviewed and analyzed. The treatment protocol consisted of IV topotecan 0.75 mg/m(2) on days 1, 2, and 3; combined with cisplatin 50 mg/m(2) IV on day 1 and repeated every 21 days until progression or unacceptable toxicity for a maximum of 6 cycles. The outcomes were evaluated based on the response rate, progression free survival (PFS), and overall survival (OS) by using the World Health Organization criteria. The adverse effects of the treatments were also determined. Twenty-one cervical cancer patients received the CT regimen. The tumor response rate was 28.6%. The median PFS and OS was 4 and 11 months, respectively. With 87 cycles of chemotherapy, the most common grade 3 & 4 hematologic toxicity was neutropenia (57.9%). Advanced and recurrent cervical cancer patients treated with cisplatin and generic topotecan had a favorable outcome with manageable toxicity.

A Phase III Trial of Paclitaxel plus Carboplatin Versus Paclitaxel plus Cisplatin in Stage IVB, Persistent or Recurrent Cervical Cancer: Gynecologic Cancer Study Group/Japan Clinical Oncology Group Study (JCOG0505)

A randomized controlled trial has been started in Japan to compare the utility of palliative chemotherapy containing paclitaxel and carboplatin (TC) with paclitaxel and cisplatin (TP) as a standard treatment for patients with the newly diagnosed Stage IVB, persistent or recurrent cervical cancer who are not amenable to curative treatment with local therapy. This trial was designed to evaluate the non-inferiority of TC as measured by the number of hospitalized days as an indicator of quality of life (QOL) when compared with TP combination therapy. The primary endpoint is overall survival. Secondary endpoints are progression-free survival, response rates, adverse events, severe adverse events and the proportion of non-hospitalization periods compared with planned treatment periods.

Phase II study of S-1 in patients with advanced or recurrent cervical cancer

5514 Background: S-1, an oral fluoropyrimidine combination drug, is active agent against many types of cancer. This phase II study was designed to evaluate the efficacy and safety of S-1 in uterine cervical cancer. This is the first clinical study of S-1 in gynecologic cancer. Methods: The subjects were women 20 to 74 years of age with stage IVB or recurrent cervical cancer who had measurable disease and had not received more than one platinum-containing regimen of chemotherapy since the diagnosis of IVB disease or recurrence. The primary endpoint was the overall response rate (ORR) according to RECIST. The study comprised two stages: 20 patients were scheduled to be enrolled in the first stage, and 15 in the second (total 35). S-1 was given twice daily for 28 days, followed by 14 days of rest. Results: A total of 37 patients were enrolled between October 2005 and April 2007. One patient was ineligible. Of the 36 eligible patients, 34 had recurrent disease, 31 had received prior radiation therapy, and 21 had received prior chemotherapy. A median of four cycles of chemotherapy was given (range: one to 17+ cycles). The ORR was 33.3% (12/36, 95% CI: 18.6% - 51.0%). The most frequent grade 3/4 toxicities were anemia (16.2%), neutropenia (8.1%), diarrhea (21.6%), and anorexia (16.2%). There were no treatment-related deaths. Conclusions: S-1 monotherapy seems highly active and well tolerated in women with advanced or recurrent carcinoma of the uterine cervix. Further studies of S-1 in women with gynecologic cancer are warranted. No significant financial relationships to disclose.

Combination therapy with carboplatin plus paclitaxel is comparable to cisplatin plus paclitaxel therapy in women with stage IVB, recurrent or persistent cervical cancer,

Combination therapy with carboplatin plus paclitaxel is comparable to cisplatin plus paclitaxel therapy in women with stage IVB, recurrent or persistent cervical cancer,

A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer

Cisplatin-based combination therapy produces higher response rates and improved survival, in comparison to single-agent cisplatin in the treatment of cervical cancer. Cisplatin and paclitaxel (PT) requires a prolonged infusion and is less convenient and more toxic than the combination of carboplatin and paclitaxel (CT) leading to more widespread use of CT. The objective of this study was to compare response rate and survival in patients with cervical cancer treated with PT or CT. A retrospective search of databases at the University of Oklahoma, Washington University-Barnes Jewish Christian Hospitals, Johns Hopkins University, and University of Alabama at Birmingham identified patients with stage IVB, recurrent or persistent cervical cancer who were treated with PT or CT. A total of 62 patients were identified. 14 were treated with PT and 48 with CT. There were no statistical differences between the groups in terms of demographics, prior radiation therapy, or median number of cycles. There was a trend toward a larger number of patients in the CT arm having received prior cisplatin/radiation (p=0.07). Objective responses occurred in 29% of patients receiving PT vs. 53% of patients receiving CT. With a median follow-up of 9 months, survival was not different with a median survival of 14 and 11 months, respectively. In this retrospective evaluation, CT compares favorably with PT and demonstrates a superior overall response rate. Because of its ease of administration and improved toxicity profile, CT should be considered in the treatment of advanced, recurrent or progressive cervical cancer.

Outcomes in 24 selected patients with stage IVB cervical cancer and excellent performance status treated with radiotherapy and chemotherapy

We sought to review outcomes in patients with stage IVB carcinoma of the cervix treated with irradiation in combination with chemotherapy. We report outcomes of 24 consecutive patients with good performance status treated from 1998 to 2005. Most of these patients underwent concurrent irradiation with platinum-based chemotherapy. Some patients received subsequent systemic chemotherapy. All patients underwent external beam radiotherapy; 7 patients (29%) had additional high-dose-rate and 12 (50%) low-dose-rate brachytherapy. Two patients (8%) received an IMRT boost instead of brachytherapy. The mean dose to point A was variable (73.9 +/- 19.2 Gy). Twenty patients (83%) received radio-sensitizing platinum-based chemotherapy, and the remaining had radiotherapy alone. Seven patients (29%) had further combination chemotherapy. Therapy was well tolerated. The overall survival was 44% at 36 months and 22% at 5 years. Patients with stage IVB cervical cancer have mostly been treated with palliative intent. With the advent of concurrent chemoradiation, we have treated many of these cases with aggressive combination therapy. In this series, the use of radiotherapy and multiagent chemotherapy in patients with stage IVB cervical carcinoma and good performance status was well tolerated and resulted in higher survival rates than previously reported.

A phase I study of ifosfamide, paclitaxel, and carboplatin in advanced and recurrent cervical cancer

Objectives. To determine toxicity and establish a maximum tolerated dose of outpatient therapy with ifosfamide, paclitaxel, and carboplatin in women with advanced and recurrent cervical cancer. Methods. Eligible patients had stage IVB, recurrent or persistent cervical cancer that was not amenable to curative treatment with surgery or radiation therapy. A dose escalation through four dose levels was planned. Dose limiting toxicities were defined as grade 3 or grade 4 hematologic toxicity persistent to day 1 of the next scheduled cycle, grade 2 or higher central neurologic symptoms related to ifosfamide and grade 3 or grade 4 peripheral neuropathy. Results. Twelve patients, aged 29 to 71, received 64 treatments and were evaluable for toxicity. No patient was withdrawn from the study due to toxicity. Two patients had received prior radiation therapy without chemotherapy, and seven patients had received radiation therapy with concurrent chemotherapy. No dose limiting toxicity occurred at dose levels 1 or 2. Three dose reductions occurred at dose level 3 due to neutropenia and thrombocytopenia. The maximum tolerated dose is ifosfamide 2 g/m 2 over 2 h, paclitaxel 175 mg/m 2 over 1 h, and carboplatin at an AUC of 5 over 45 min. Grade 3 or grade 4 neutropenia was seen in 11 subjects. Two patients required growth factor support. Grade 3 or grade 4 anemia was seen in one patient. Grade 3 or grade 4 neuropathy was seen in one patient. Other grade 3 or grade 4 non-hematologic toxicity included muscle weakness, myalgia, cough, and shortness of breath. Conclusions. Combination therapy with ifosfamide 2 g/m 2, paclitaxel 175 mg/m 2, carboplatin AUC = 5 appears to be a safe regimen for the outpatient treatment of women with advanced or recurrent cervical cancer and warrants phase II investigation.

温熱放射線治療抵抗性子宮頸癌に関与するHIF1A遺伝子

Microarray profiling is a powerful approach to identify individual genes that may have important functions of a neoplasm. To identify a set of genes related to thermoradioresistancy of cervical carcinoma, we investigated a total of 19 patients with Stage IIIA to Stage IVB cervical cancer who underwent definitive thermoradiotherapy between May 1995 and August 2001. We compared the expression profiles of 8 thermoradiosensitive and 11 thermoradioresistant tumors obtained by punch biopsy before treatment using a cDNA microarray consisting of 23, 040 human genes. We selected 35 genes on the basis of a clustering analysis. One of these genes in thermoradioresistant tumors was already known to be associated with hypoxia-inducible factor 1A (HIF1A) that regulates the expression of a variety of genes encoding proteins related to angiogenesis and to anaerobic metabolism of cells exposed to hypoxic stress.These results suggested that HIF1A gene might play a role of thermoradioresistancy in advanced-stage cervical carcinoma.

Detection of human papillomavirus mRNA and cervical cancer cells in peripheral blood of cervical cancer patients with metastasis.

To determine the presence of cervical cancer cells in circulating peripheral blood of stage IVb cervical cancer patients with metastasis to distant organs. Cervical cancer tissue from 15 stage IVb cervical cancer patients with metastasis were analyzed for the presence of human papillomavirus (HPV) type 16 DNA by nested polymerase chain reaction (PCR). The presence of transcriptional products of the HPV type 16 E6-transforming gene in the peripheral blood of the same 15 cancer patients was analyzed by reverse transcription and PCR. Cervical tissues and peripheral-blood specimens from 12 normal healthy individuals served as controls. Thirteen of 15 (86.7%) cervical cancer tissues from same number of patients were found to contain HPV type 16 DNA. Peripheral-blood specimens from 12 of 13 (92.3%) cervical HPV DNA-positive patients were found to contain HPV-specific mRNA detectable by reverse transcription (RT) and PCR. Cervical tissues from all 12 normal controls were HPV-free. None of the peripheral-blood specimens from two cervical HPV-negative cancer patients and 12 normal controls contained detectable amounts of mRNA of HPV type 16 E6-transforming gene. The most likely source of the HPV-specific mRNA detected in the peripheral blood of cervical cancer patients with metastasis is the cervical cancer cells derived from or shed from the cervix. The presence of HPV E6 mRNAs in peripheral blood may be a sensitive indicator of circulating cervical cancer cells. If PCR positivity is proven to be able to predict disease progression reliably, these findings may have clinical applications in the treatment of cervical and many other cancers.