Recurrent Uterine Cervical Cancer Research Articles

KORTUC, a novel hydrogen peroxide‑based radiosensitizer for the enhancement of brachytherapy in patients with unresectable recurrent uterine cervical cancer.

Kochi Oxydol Radiation Therapy for Unresectable Carcinoma (KORTUC) is a novel radiosensitizer invented by Professor Ogawa at Kochi University (Japan) in 2006. The current study aimed to report the experience of the present authors with the use of KORTUC treatment in combination with interstitial brachytherapy (ISBT), with or without external beam (EB) radiotherapy (RT), in patients with locally recurrent cervical cancer (LRCC), who were likely to have a high risk of poor prognosis. Between April 2012 and January 2020, 14 female patients (15 tumoral lesions) with LRCC underwent KORTUC with ISBT. Their previous treatments included surgery (n=4), radiation therapy (n=8) and surgery plus RT (n=3). The primary lesions were located in the vaginal stump (n=5), pelvic wall (n=3), cervix (n=3), vaginal wall (n=2) and lymph nodes (n=2). At 2 h before RT, KORTUC was injected intratumorally via direct colposcopy. The dose of KORTUC ranged from 4-12 ml, adjusted for the tumor size. For patients who underwent ISBT, KORTUC was administered before and after insertion of the applicator before irradiation. Intratumoral injection of KORTUC was completed without any technical or safety issues in all 15 patients; it was well tolerated with no adverse events observed. KORTUC also showed preferable efficacy; a clinical complete response was observed in 87% of patients and the initial response rate was 100%. The 2-year local control rate in patients who underwent ISBT + KORTUC was 79%, whereas it was 63% in the re-irradiation group which was significantly lower (P=0.02) than that in the non-irradiation group (100%). Based on this finding, KORTUC with external irradiation is considered to be an optimal treatment strategy for patients with newly diagnosed LRCC this disease. Additionally, KORTUC may be an effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

CLEFMA induces intrinsic and extrinsic apoptotic pathways through ERK1/2 and p38 signalling in uterine cervical cancer cells.

Although concurrent chemoradiotherapy is the cornerstone of treatment for locally advanced or recurrent uterine cervical cancer, treatment fails at a high rate. Therefore, the development of novel targeting agents is critical. This study investigated the action of CLEFMA, a potent, synthetic curcumin derivative, on cervical cancer cells and its mechanism of action. We found that CLEFMA negatively regulated the viability of cervical cancer cells, involving induction of cell apoptosis. Cleaved caspase-3, cleaved poly(adenosine diphosphate-ribose) polymerase, cleaved caspase-8, and cleaved caspase-9 expression were increased by treatment with CLEFMA. After U0126 (ERK1/2 inhibitor) and SB203580 (p38 inhibitor) were applied as cotreatment with CLEFMA, the expression of cleaved caspase-8, -9, and -3 was reduced significantly. In conclusion, CLEFMA activates both extrinsic and intrinsic apoptotic pathways through ERK1/2 and p38 signal transduction in cervical cancer cells.

GSOR22 Presentation Time: 12:15 PM: A Novel Radiosensitizer Kortuc Enhanced Brachytherapy for Unresectable Recurrent Uterine Cervical Cancer

<h3>Purpose</h3> To evaluate the tolerability, safety and efficacy of KORTUC Intratumoral injection with brachytherapy in unresectable recurrent cervical cancer. <h3>Materials and Methods</h3> A novel radiosensitizer KORTUC (Kochi Oxydol Radiation Therapy for Unresectable Carcinoma) was invested by Dr. Yasuhiro Ogawa at Kochi University (Japan) in 2006 and was developed for the treatment of malignant solid tumours that contain numerous hypoxic cancer cells and/or large quantities of antioxidative enzymes. Hydrogen peroxide is the only agent known to be capable of inactivating antioxidative enzymes and producing oxygen simultaneously when applied to tumour tissues. KORTUC is a solution that contains 3% hydrogen peroxide with 1% sodium hyaluronate. Hydrogen peroxide is the active ingredient for this radiosensitizer. Sodium hyaluronate viscosity sustains the hydrogen peroxide in the tumour as well as delays decomposition of hydrogen peroxide and maintains a high concentration of oxygen in the tumour. Injecting the two components together at a particular ratio is the key feature of this product. Currently Phase 2 clinical trial for locally advanced and recurrent breast cancer has been conducted in the United Kingdom and India. Our institution, (Osaka Medical and Pharmaceutical University, Japan) has conducted single-arm clinical research of KORTUC since May 2010, we dosed KORTUC more than 250 patients of various solid cancers including more than 40 patients of the gynecological tumors treated with brachytherapy as of today. In this study we report our experiences of KORTUC with brachytherapy in recurrent local advanced cervical cancer patients who are likely the high risk of poor prognosis.From April 2012 to January 2020, 15 female patients with recurrent cervical cancer received KORTUC with brachytherapy. Previous treatments of 15 recurrent patients were surgery (n=4), radiation therapy (n=8), surgery + radiation therapy (n=3). The primary lesion of these 15 patients were vaginal stump (n=5), pelvic wall (n=3), cervix (n=3), vaginal wall (n=2), and lymph node (n=2). KORTUC was injected intratumorally under direct vision of colposcopy prior to radiation therapy. The dose of KORTUC ranged from 4 to 12 mL adjusted by tumor size. For patients who had the Interstitial brachytherapy, KORTUC was administered before and after the applicator insertion prior to irradiation. <h3>Results</h3> Intratumoral injection of KORTUC was completed without any technical and safety issues in all 15 patients. KORTUC was well tolerated and no adverse events judged to be related to KORTUC injection were observed, except the transient local pain at the injection site in some patients. KORTUC also showed efficacy in local control in recurrent patients. <h3>Conclusion</h3> Based on this result, we would like to confirm in a future study, KORTUC's efficacy with external irradiation as well as brachytherapy for the newly diagnosed unresectable locally advanced cervical cancer with high risk factors of poor prognosis. KORTUC may have potential as an effective radiation response enhancer in multiple cancer types in which locoregional control after RT alone remains poor.

Efficacy of local salvage therapy for recurrent uterine cervical cancer after definitive radiotherapy.

The prognosis of patients with recurrence of uterine cervical cancer after definitive radiotherapy and the efficacy of local salvage therapy for recurrence were evaluated. We retrospectively reviewed 110 patients who were treated with definitive radiotherapy/chemoradiotherapy for uterine cervical cancer between 2008 and 2017 at our institution. Local salvage therapy was defined as any surgery or radiotherapy described in the medical record as intended for local control or cure. We identified 25 patients who developed recurrence after definitive radiotherapy/chemoradiotherapy. The median follow-up time post-recurrence was 18.9months. Thirteen patients (52%) reported recurrence in the isolated extra-pelvic lymph node (EPLN). The 2-year overall survival after first recurrence (OSr) for patients with isolated EPLN recurrence was 83.1%, compared to that of 31.2% for patients with other patterns of recurrence (p < 0.001). The 2-year OSr for patients who underwent local salvage therapy was 75.2%, whereas that for patients who did not undergo therapy was 41.6% (p = 0.04). Among patients who had recurrence in the isolated EPLN and received local salvage therapy, 20% of the patients reported recurrence in visceral and/or bone metastases after local salvage therapy, and 50% of the patients experienced another EPLN recurrence, which was salvaged with repeating local therapy. Patients with uterine cervical cancer with isolated EPLN recurrence had favorable prognoses. The indications of local salvage therapy should be considered, especially for patients with isolated EPLN recurrence.

Renal Subcapsular Hematoma Formation Due to Hydronephrosis Caused by Recurrent Uterine Cervical Cancer

Most non-traumatic renal subcapsular hematomas are found in the presence of primary or metastatic renal tumors, or in the presence of vascular disease of the renal blood vessels. We managed an asymptomatic renal subcapsular hematoma that formed due to uterine cervical cancer that metastasized to the left common iliac lymph nodes. A 48-year-old woman with stage IB1 cervical cancer underwent neoadjuvant chemotherapy and concurrent chemoradiation following a radical hysterectomy. Six months after the completion of her first treatment, she developed left-sided hydronephrosis, a left subcapsular hematoma and left common iliac lymph nodes enlargement as demonstrated with contrast-enhanced computed tomography. Although a renal subcapsular hematoma is rarely a symptom of cervical cancer recurrence, it should be considered if other neoplastic or vascular diseases are ruled out. J Med Cases. 2021;12(3):126-129 doi: https://doi.org/10.14740/jmc3640

Efficacy Of Metastasis-Directed Therapy For Recurrent Uterine Cervical Cancer After Definitive Radiotherapy

Efficacy Of Metastasis-Directed Therapy For Recurrent Uterine Cervical Cancer After Definitive Radiotherapy

Image-guided interstitial high-dose-rate brachytherapy for locally recurrent uterine cervical cancer: A single-institution study

PurposeThe aim of this study was to investigate the efficacy and safety of image-guided high-dose-rate (HDR) interstitial brachytherapy (ISBT) for reirradiation of locally recurrent uterine cervical cancer. Methods and MaterialsBetween 2008 and 2015, patients receiving reirradiation using HDR-ISBT for local gross recurrence of uterine cervical cancer after definitive or postoperative radiotherapy were analyzed retrospectively. The prescription doses per fraction ranged 2.5–6.0 Gy, whereas the cumulative equivalent doses in 2 Gy fractions ranged 48.6–82.5 Gy. The effects of prognostic factors on the local control (LC), progression-free survival, and overall survival were analyzed, and late toxicity data were evaluated. ResultsEighteen patients were included in the analysis, with a median followup of 18.1 months. A tumor response was obtained in all patients, with radiological and pathological complete remission seen in 12 (66.7%) patients. The 2-year LC, progression-free survival, and overall survival rates for all patients were 51.3%, 20.0%, and 60.8%, respectively. The hemoglobin level and maximum tumor diameter were shown to be statistically significant prognostic factors for LC (p = 0.028 and 0.009, respectively). Late ≥ Grade 2 adverse events were observed in 5 patients (27.8%). ConclusionsImage-guided HDR-ISBT for the reirradiation of locally recurrent uterine cervical cancer may play an important role for local tumor control in a subgroup of patients. However, the treatment indication must be weighed against the risk of higher-grade late toxicity.

Feasibility study on combination chemotherapy using nogitecan hydrochloride (topotecan) and cisplatin for patients with metastatic, persistent, or recurrent uterine cervical cancer

The standard chemotherapeutic regimen for stage IVB, persistent, or recurrent uterine cervical cancer is platinum-based combination chemotherapy such as cisplatin (CDDP)/paclitaxel and CDDP/nogitecan hydrochloride (NGT, topotecan). Because it is unclear whether the CDDP/NGT combination chemotherapy is tolerable for Japanese patients, we conducted the present study to assess the feasibility of CDDP/NGT combination chemotherapy. Between June 2012 and April 2014, 15 patients with stage IVB, persistent, or recurrent uterine cervical cancer were enrolled in this study. Patients underwent six cycles of NGT at a dose of 0.75mg/m2, followed immediately by CDDP at a dose of 50mg/m2 on day 1 by intravenous infusion, and then NGT at a dose of 0.75mg/m2 on days 2 and 3. Of 15 patients, 9 patients underwent at least 6 cycles of NGT/CDDP combination chemotherapy. Of a total of 83 cycles, 70 cycles (84.3%) of NGT/CDDP combination chemotherapy could be continued at the starting dose of NGT (0.75mg/m2). Grade 3/4 hematological toxicities included leukopenia in 10 patients (66.7%), neutropenia in 15 (100%), anemia in 6 (40.0%), thrombocytopenia in 4 (26.7%), and febrile neutropenia in 4 (26.7%). The response rate according to RECIST was 27% (3/11), with partial response in 3 patients. NGT/CDDP combination chemotherapy may be a tolerable and effective regimen for Japanese patients with stage IVB, persistent, or recurrent uterine cervical cancer. Based on the results of this study, NGT/CDDP combination chemotherapy was approved in Japan in November 2015.

Metastatic Thyroid Gland Tumor Presenting as an Initial Manifestation of Recurrent Uterine Cervical Cancer

비록 자궁경부암이 ê°‘ìƒì„ ìœ¼ë¡œì˜ ì „ì´ëŠ” 매우 드물지만, 자궁경부암의 ê³¼ê±°ë ¥ì´ 있는 경우, ê°‘ìƒì„ ë¶€ìœ„ì˜ ë¶€ì¢ ì´ë‚˜ 촉지되는 ê²°ì ˆì´ 발생하면 반드시 ì „ì´ì„± 병변을 의심해봐야 한다. 비록 ê°‘ìƒì„ ìœ¼ë¡œì˜ ì „ì´ëŠ” 매우 나쁜 예후를 의미하지만 ê³ ì‹ì  치료로 ì „ì‹ í•­ì•”ìš”ë²• 및 ë°©ì‚¬ì„ ìš”ë²•ì´ 환자의 삶의 질 ê°œì„ ì— 도움을 줄 수 있다. 드물기는 하지만 ê°‘ìƒì„ ìœ¼ë¡œì˜ ì• ì„±ì „ì´ ë³´ê³ ê°€ 증가하는 추세로, 이에 대해 ì–´ë– í•œ 치료가 가장 íš¨ê³¼ì ì¼ì§€ì— 대한 연구가 í•„ìš”í•˜ê² ë‹¤. 중심 단어: ê°‘ìƒì„ ì•”; 자궁경부암; 재발

Value of 18F-FDG PET/CT in patients with cancer of the uterine cervix having elevated serum squamous cell carcinoma antigen after treatment

Objective To evaluate the clinical value of 18F-FDG PET/CT in the detection of residual, recurrent and metastatic diseases in post-treatment uterine cervical cancer patients presenting with elevated serum squamous cell carcinoma (SCC) antigen levels. Methods Between March 2009 and October 2012, 18F-FDG PET/CT was performed in 48 patients(average age (47.5±11.2) years) with suspected residual, recurrent or metastatic uterine cervical cancer because of increased serum SCC antigen level (>1.5 μg/L). The final diagnosis was established by pathology or more than 1 year of clinical follow-up. The diagnostic efficiency of 18F-FDG PET/CT was calculated. Two-sample t test was used for data analysis. Results The serum SCC levels were 1.6-42.5(mean: 8.6±9.4) μg/L. Among the 48 patients, 45 (93.75%) were confirmed of having malignant lesions. 18F-FDG PET/CT along with other imaging detected 174 lesions, of which 169 were proven as residual, recurrent or metastatic diseases. 18F-FDG PET/CT correctly identified 159 lesions, yielding a diagnostic sensitivity and accuracy of 94.08%(159/169) and 91.38%(159/174), respectively. The diagnostic sensitivity and accuracy for residual and recurrent diseases were both 9/10; for lymph node metastasis were 94.59%(105/111) and 92.92%(105/113), respectively; and for other sites of metastasis were 93.75% (45/48) and 88.24%(45/51), respectively. There was no significant difference of SUVmax between the patients with residual/recurrent disease (mean: 6.9±3.8, range: 2.0-13.7) and those with metastasis (mean: 6.3±2.7, range: 2.0-14.4,t=0.629, P>0.05). Conclusion 18F-FDG PET/CT is valuable for the detection of residual, recurrent and metastatic diseases in the uterine cervical cancer patients presenting with elevated serum squamous cell carcinoma antigen after conventional treatment. Key words: Cervix neoplasms; Neoplasm recurrence, local; Neoplasm metastasis; Antigens; Tomography, emission-computed; Tomography, X-ray computed; Deoxyglucose

Feasibility and Safety of Negative-Balance Isolated Pelvic Perfusion in Patients with Pretreated Recurrent or Persistent Uterine Cervical Cancer.

Second-line therapy has limited activity in patients with recurrent or persistent uterine cervical cancer that has progressed after chemoradiation and palliative chemotherapy. The purpose of this study was to evaluate the efficacy of negative-balance isolated pelvic perfusion (NIPP) in patients with pretreated recurrent/persistent uterine cervical cancer. Between April 2004 and May 2013, a total of 26 patients with recurrent or persistent uterine cervical cancer previously treated with platinum-based systemic chemotherapy and/or chemoradiotherapy received NIPP therapy at our institution, consisting of a 30-min isolated pelvic perfusion with cisplatin and fluorouracil, followed by isolated pelvic dialysis. Primary endpoints were response rate (RR) and progression-free survival (PFS), while secondary endpoints were overall survival (OS) and safety. Platinum pharmacokinetics were also evaluated. The RR was 57.7 % (complete response, five patients; partial response, ten patients). The median PFS and OS after NIPP therapy were 11.0 (95 % confidence interval [CI] 6.6-15.4) and 25.1 (95 % CI 17.1-33.1) months, respectively. PFS was significantly better in patients without intestinal involvement (p = 0.016) or dissemination (p < 0.001). Survival rates at 1, 2, and 3 years after initial NIPP therapy were 65.2, 50.4, and 13.4 %, respectively. The plasma pelvic-to-systemic exposure ratios were 15.4 and 15.8, based on the maximum concentration and the concentration-time curve, respectively. Most adverse events were mild (grade 1-2) (Common Terminology Criteria for Adverse Events, version 3.0). Severe neutropenia (grade 3 or higher) occurred in only 7.7 % of patients. NIPP appears to be an effective and feasible method for patients with pretreated recurrent or persistent cervical cancer.

Prognostic factors for curative pelvic exenterations in patients with recurrent uterine cervical or vaginal cancer.

The aim of this study was to assess the prognostic factors after curative pelvic exenterations performed for recurrent uterine cervical or vaginal cancers in the era of concomitant chemoradiotherapy. We retrospectively enrolled 16 patients with recurrent uterine cervical or vaginal cancer and tumor-free resection margins on pelvic exenteration pathological analysis between October 1997 and April 2014. Pelvic exenterations were performed for 13 recurrent cervical cancers and 3 recurrent vaginal cancers. All of the patients had received pelvic irradiation (external radiotherapy for 14 patients and brachytherapy for 2 patients). The median age at the recurrence was 59.5 years (49-77 years), and the median tumor size was 4.35 cm (2-9 cm). There were no intraoperative or postoperative deaths. The 5-year disease-free survival and overall survival were 30% and 34.1%, respectively. The following 3 factors affected the disease-free survival: tumor size greater than 5 cm (P = 0.05), mesorectal lymph node involvement (P = 0.02), and vascular emboli (P = 0.0093). The presence of vascular emboli is a new prognostic factor in cases of recurrent cervical or vaginal cancer. Assessing the presence of vascular emboli on pretherapeutic biopsies could facilitate the selection of patients eligible for curative pelvic exenterations.

Salvage stereotactic body radiotherapy for locally recurrent uterine cervix cancer at the pelvic sidewall: Feasibility and complication.

To determine the feasibility of stereotactic body radiotherapy (SBRT) in patients with pelvic sidewall recurrence of uterine cervical cancer after radical hysterectomy or definitive radiotherapy. We retrospectively reviewed 23 patients with locally recurrent uterine cervical cancer limited to the pelvic sidewall who were treated with SBRT at our institution between January 2003 and May 2010. The SBRT dose ranged from 27 to 45 Gy (median, 39 Gy) in three fractions, and the fractional SBRT dose ranged from 9 to 15 Gy (median, 13 Gy). The 2-year overall survival, local progression-free survival and disease progression-free survival rates were 43%, 65% and 52%, respectively. Patients with small tumors (gross tumor volume <30 cm(3) ) had a significantly longer 2-year overall survival rate and 2-year local progression-free survival rate than did patients with large tumors (overall survival rate: 89% vs 12%; P = 0.0001 and local progression-free survival: 85% vs 0%; P = 0.0199). There were three cases (13%) of severe toxicities (rectovaginal fistula). Pelvic pain relief was achieved in all patients. In particular, 10 of 14 patients (71%) achieved analgesic (nonsteroidal anti-inflammatory drug or narcotic) reduction of 50% or more from baseline. SBRT is a feasible treatment option for women with pelvic sidewall tumors from recurrent uterine cervical cancer, especially for small recurrent tumors. However, SBRT should be used carefully in the treatment of large tumors, as the incidence of severe late toxicity increases with the size of the tumor.

Diagnosis of recurrent uterine cervical cancer: PET versus PET/CT: a systematic review and meta-analysis.

The aim of this work was to assess and compare the overall value of stand-alone FDG PET and PET/CT in diagnosing recurrent cervical cancer with a meta-analysis. All the English published studies which addressed the use of PET whether interpreted with or without the use of CT for the diagnosis of recurrent cervical cancer were collected. Methodological quality of the included studies was evaluated. Pooled sensitivity and specificity were calculated, summary receiver operating characteristics (SROC) curve analysis was used to compare the diagnostic ability of stand-alone PET and PET/CT. A total of 18 studies were included in this meta-analysis, with a total of 762 subjects. Pooled sensitivity and specificity of PET and PET/CT were 0.91 (95% CI 0.87-0.94) and 0.94 (95% CI 0.89-0.97), and 0.92 (95% CI 0.91-0.94) and 0.84 (95% CI 0.74-0.91), respectively. The areas under the SROC curve (AUCs) of PET and PET/CT were 0.9610 and 0.9491, respectively. There was no statistical significance between the AUC of PET and PET/CT (P>0.05). Both PET and PET/CT have good performance in the detection of recurrent cervical cancer. However, interpreted CT images may have limited additional value on PET in detecting recurrent cervical cancer.

A pilot feasibility study for cisplatin plus S-1 for the treatment for advanced or recurrent cervical cancer

To evaluate the feasibility of a cisplatin and S-1 combination regimen for the treatment for metastatic and recurrent cervical cancers, we performed this study prior to a randomized phase III trial to evaluate the clinical benefits of a cisplatin and S-1 combination regimen compared with cisplatin alone. Cisplatin (50 mg/m(2), intravenously on day 1) and S-1 (80-120 mg/m(2), orally twice a day between days 1 and 14) were administered every 21 days for 6 cycles in patients with advanced or recurrent uterine cervical cancer. A total of 10 patients were enrolled in this trial. A total of 46 treatment cycles (median 6; range 1-6) were administered. All grade 3 or 4 hematologic toxicities were recorded in the 6 patients: 2 patients experienced anemia, 5 experienced neutropenia, 1 experienced thrombocytopenia, and 2 experienced febrile neutropenia. All grade 3 non-hematologic toxicities were recorded in the 6 patients, and no grade 4 non-hematologic toxicities occurred; the most frequent toxicities were hyponatremia in 3 patients, diarrhea in 2 patients, and infection in 2 patients. The patients with grade 3 diarrhea had received prior radiotherapy. All the patients recovered from the toxicities after receiving appropriate supportive care, and no treatment-related deaths occurred. Five patients (50 %) achieved a partial response, and 1 patient (10 %) had a stable disease. A cisplatin and S-1 combination regimen was feasible for patients with recurrent cervical cancer. Since patients who receive prior radiotherapy may experience severe diarrhea, these patients may require an S-1 dose reduction.

Clinical outcome of pelvic exenteration in patients with advanced or recurrent uterine cervical cancer

Pelvic exenteration has attained an important role in the treatment of advanced or recurrent cervical cancer for obtaining a complete cure or longer disease-free survival. The purpose of this study was to evaluate patients undergoing pelvic exenteration and to determine the clinical features associated with outcome and survival. We retrospectively analyzed the records of 12 patients who underwent pelvic exenteration for uterine cervical cancer between July 2002 and August 2011. Two patients had primary stage IVA cervical adenocarcinoma and 10 patients had recurrent cervical cancer. Eight patients underwent anterior pelvic exenteration, 3 patients underwent total pelvic exenteration, and 1 patient underwent posterior pelvic exenteration. With a median duration of follow-up of 22 months (range 3-116 months), 5 patients were alive without recurrence. Of 5 patients with no evidence of disease, 4 were recurrent or residual tumor, all of whom had common factors, such as a tumor size ≤ 30 mm, negative surgical margins, complete resection, and no lymph node involvement. The 5-year overall survival rate for 12 patients was 42.2 %. Ileus was the most common complication (42 %) and post-operative intestinal anastomosis leaks developed in 3 patients, but no ureteral anastomosis leaks occurred. Pelvic exenteration is a feasible surgical procedure in advanced and/or recurrent cervical cancer patients with no associated post-operative mortality, and the only therapeutic option for complete cure or long-term survival; however, post-operative complications frequently occur.

Combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer

The clinical activity of combination of irinotecan (CPT-11) and nedaplatin (NDP) for recurrent patients with uterine cervical cancer was evaluated retrospectively. Intravenous CPT-11 was given at 60mg/m(2) (days 1, 8, 15), followed by NDP 80mg/m(2) (day 1), every 4weeks. According to the medical records, 29 cases have received this regimen since 2000. Median age was 57years (range, 29-80), and performance status (PS) of the patients was 18 cases with PS 0, 10 cases with PS 1, and 1 case with PS 2, respectively. Clinical stage was as follows: 3 cases of stage Ib1, 2 cases of Ib2, 2 cases of IIa, 10 cases of IIb, 8 cases of IIIb, and 4 cases of IVb. There were 27 cases of squamous cell carcinoma and 2 cases of adenocarcinoma. Concerning hematological toxicity of grade 3 or more, neutropenia, leukopenia, and febrile neutropenia were observed in 79.3%, 96.6%, and 13.8% of cases, respectively. For nonhematological toxicity, nausea, anorexia, joint pain, and confusion were observed in only 1 case, respectively, and as a result, in 7 cases chemotherapy was not completed. Among 26 cases with clinically evaluable lesions, there were 7 complete responses, 3 partial responses, 7 stable disease, and 9 progressive disease; the clinical response rate was 38.5%. Median progression-free survival was 7months (range, 0-38months). The combination of CPT-11 and NDP seems to be active for patients with recurrent uterine 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.

Conditionally replicating E1B-deleted adenovirus driven by the squamous cell carcinoma antigen 2 promoter for uterine cervical cancer therapy

Cervical cancer is the second most common type of malignant tumor among women worldwide. When the disease is confined locally, it can be controlled with surgical resection and radiotherapy. However, patients with recurrent or metastatic disease often have a poor prognosis. Measurement of serum levels of squamous cell carcinoma (SCC) antigens has been widely used as serological markers for SCC of uterine cervix. Recently, it has been demonstrated that cervical cancer patients with elevated squamous cell carcinoma antigen-2 (SCCA2) expression in tumor cells carry a poor prognosis. Here, by using a luciferase reporter assay, we show that SCCA2 promoter was active in SCCA2-producing human cervical cancer cell lines, including Cx, Cxwj, SiHa and HeLa cells, but relatively quiescent in normal cervical epithelial cells. We then developed a conditionally replicating adenovirus, designated Ad-KFH, under the transcriptional control of the SCCA2 promoter. This E1B-55 kDa-deleted oncolytic adenovirus replicated specifically in and lysed SCCA2-producing cervical cancer cells. Furthermore, in a peritoneal metastatic tumor model, Ad-KFH retarded Cxwj tumor growth in NOD/severe combined immunodeficient mice and prolonged survival of tumor-bearing mice, especially when combined with cisplatin. These results suggest that Ad-KFH may provide a new strategy of gene therapy for advanced or recurrent uterine cervical cancer.

Performance of FDG-PET/CT for diagnosis of recurrent uterine cervical cancer

The purpose is to evaluate the accuracy of integrated FDG-PET/CT, compared with PET alone, for diagnosis of suspected recurrence of uterine cervical cancer. Fifty-two women who had undergone treatment for histopathologically proven cervical cancer received PET/CT with suspected recurrence. PET-alone and integrated PET/CT images were evaluated by two different experienced radiologists by consensus for each investigation. A final diagnosis was confirmed by histopathology, radiological imaging, and clinical follow-up for over 1 year. Patient-based analysis showed that the sensitivity, specificity, and accuracy of PET/CT were 92.0% (23/25), 92.6% (25/27), and 92.3% (48/52), respectively, while for PET, the corresponding figures were 80.0% (20/25), 77.8% (21/27), and 78.8% (41/52), respectively. PET/CT resolved the false-positive PET results due to hypermetabolic activity of benign/inflammatory lesions and physiological variants, and was able to detect lung metastasis, local recurrence, peritoneal dissemination, para-aortic lymph node metastasis, and pelvic lymph node metastasis missed by PET alone. However, tiny local recurrence and lymph node metastasis could not be detected even by PET/CT. FDG-PET/CT is a useful complementary modality for providing good anatomic and functional localization of sites of recurrence during follow-up of patients with cervical cancer.