Efficacy of paclitaxel and carboplatin as a regimen for postoperative concurrent chemoradiotherapy of high risk uterine cervix cancer

OBJECTIVE: To evaluate the efficacy and safety of concurrent chemoradiotherapy with paclitaxel and carboplatin after hysterectomy for early stage uterine cervical carcinoma with high risk factors. METHODS: Between March 2000 and July 2002, 37 patients with stages IB-IIB uterine cervical carcinoma were treated with radical hysterectomy and bilateral pelvic lymph node dissection followed by concurrent chemoradiotherapy (POCCRT) with two courses of paclitaxel (135 mg/m(2)) and carboplatin (area under the time-concentration curve 4.5 mg min/ml) at 4-week interval. All the patients received external beam radiotherapy up to 50.4 Gy to the whole pelvis. Among these, 7 patients with close or involved resection margin received boost irradiation to the vaginal cuff (4 patients with low dose rate brachytherapy and 3 patients with external beam). Median dose of boost irradiation was 14.4 Gy (range: 14.4-34.6). RESULTS: Toxicity to POCCRT was mainly hematological and gastrointestinal, mostly grades 1 and 2. At a median follow-up of 27 months (range; 10-46), all the patients achieved local control, and 4 patients experienced distant relapses. The failure sites were as follows: bone (2 patients), paraaortic lymph node (1 patient), and supraclavicular lymph node (1 patient). CONCLUSIONS: Concurrent chemoradiotherapy with paclitaxel and carboplatin after hysterectomy is well tolerated and produces excellent local control rate despite of short follow-up period. This regimen could be considered for a phase III trial.     

Phase I clinical trial of weekly paclitaxel, weekly carboplatin, and concurrent radiotherapy for primary cervical cancer

OBJECTIVES: Standard primary treatment for locally advanced cervix cancer is radiation (RT) with concomitant platinum-based chemotherapy (CT). Incomplete local control and the appearance of distant disease herald poor survival and warrant evaluation of new primary strategies. Paclitaxel and carboplatin are active agents in recurrent cervical carcinoma, have potent, synergistic in vitro radiosensitization, and are cytotoxic in weekly schedules. This study was done to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly paclitaxel/carboplatin chemoradiotherapy in locally advanced cervix cancer. METHODS: Women with primary, previously untreated, squamous cell or adenocarcinoma of the cervix, FIGO stage IB(2) to IVA, negative para-aortic lymph nodes, adequate organ function and performance status were eligible. Pelvic RT (45 Gy over 5 weeks--180 cGy/day, four-field) was followed by two brachytherapy applications (Point A low dose rate (LDR): 90 Gy, high dose rate (HDR): 75 Gy). Concurrent weekly CT was paclitaxel 50 mg/m(2) and carboplatin, starting at AUC 1.5 and escalating in three-patient cohorts by AUC 0.5 (Max AUC 3.5). Dose escalation followed a 4-week observation period for toxicity. A grade III-IV toxicity prompted up to three additional patients per dose level. A second event defined DLT. CT was administered concurrently throughout brachytherapy. RESULTS: Fifteen patients were enrolled and treated over four dose levels until DLT was reached. Median age was 44 years (range, 23-70); stages: IB2: 1, IIB: 9, IIIA: 1, IIIB: 4. Median RT treatment time was 61 days (range, 55-79). Fourteen patients received brachytherapy (LDR: 8, HDR: 6), and one received external RT only due to cervical stenosis. The median number of weekly CT cycles was seven (range, 6-7). One CT dose was dropped in one patient for a grade II thrombocytopenia. One grade III ANC was observed at dose level II (AUC 2.0) but not seen in three additional patients. At dose level IV (AUC 3.0), two grade III-IV ANC toxicities were observed in two patients (DLT). Nine patients had grade II anemia. One patient had grade III anemia. Grade III/IV nonhematologic toxicity was rare (1/15 GI-nausea/vomiting, 1/15 pneumonia, 1/15 hypokalemia). The MTD of carboplatin is AUC 2.5 with paclitaxel 50 mg/m(2). Median follow-up is 17 months; three patients have recurred and two have died. The estimated 2-year PFS and OS are 80% and 86%. CONCLUSIONS: Weekly paclitaxel and carboplatin chemoradiation is feasible and active. The MTD for a phase II trial is 50 mg/m(2) and AUC 2.5, respectively.     

Concurrent chemoradiotherapy using high-dose-rate intracavitary brachytherapy for uterine cervical cancer

OBJECTIVE: We retrospectively reviewed our experience with concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) to assess its feasibility and efficacy in the treatment of patients with uterine cervical cancer. METHODS: Forty patients with uterine cervical squamous cell carcinoma treated with CCRT using HDR-ICBT were analyzed. The median cervical tumor size assessed by MRI was 63 mm (range: 40-86 mm). Eighteen patients (45%) had enlarged pelvic nodes on MRI (> or =10 mm). Cisplatin (20 mg/m2/day) was concurrently administered with radiotherapy for 5 days at 21-day intervals for a median of three courses (range: 1-5 courses). Thirty-eight (95%) patients received whole pelvic external beam radiotherapy (EBRT) with 40 Gy/20 fractions followed by HDR-ICBT with 18 Gy/3 fractions to point A. Subsequently, additional pelvic EBRT with 10 Gy/5 fractions was delivered with a midline block. The cumulative biological effective dose (BED) at point A of this schedule was 77 Gy10. The median follow-up period for all 40 patients was 37 months (range: 8-71 months). RESULTS: Grade 3/4 leukopenia was the most common acute side effect (83%). The actuarial 3-year pelvic control rate, disease-free survival rate, and overall survival rate were 91%, 67%, and 79%, respectively. Eight (20%) patients suffered late gastrointestinal complications (all grades). No patient suffered radiation cystitis (all grades). Only one patient experienced grade 3 complication (enterocolitis). The actuarial 3-year late complication rate (all grades) was 9% for proctitis and 15% for enterocolitis. CONCLUSION: This preliminary study suggests that CCRT using HDR-ICBT is feasible and efficacious for patients with locoregionally advanced uterine cervical cancer.     

Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy for women with locally advanced carcinoma of the uterine cervix--final results of a prospective phase II-study

OBJECTIVES: To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose rate brachyradiotherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell carcinoma (LASCC) or adeno/adenosquamous carcinoma of the uterine cervix. METHODS: Sixty-two patients with primary uterine cervical cancer were enrolled between August 1999 and November 2004. The patients had to have FIGO-stage IB2 bulky to IVA disease, biopsy-proven squamous cell or adeno/adenosquamous carcinoma of the uterine cervix. The patients were to receive external radiotherapy (50 Gy in 25 fractions); ifosfamide 2 g/m2 plus cisplatin 75 mg/m2 was applied concomitantly during two low-dose rate brachyradiotherapy applications; the planned dose to point A was 85 Gy in total. After the completion of radiotherapy, i.e. external and concomitant chemobrachyradiotherapy, four cycles of consolidation chemotherapy with the same drug combination were to be administered. RESULTS: The clinical complete response rate according to WHO-classification (assessed after the completion of the whole treatment procedures by gynecologic and radiologic evaluation and cervical biopsy) was 100%. After a median follow-up of 49 months (range 11-74 months), the recurrence-free and overall survival rates were 88.7%, respectively. The most frequent early toxicities were grade 3 and 4 leukopenias occurring in 25% and 11% of the cycles, respectively. Major delayed local complications occurred in 10 patients (16.1%). CONCLUSION: These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy with the same drug combination is a highly efficacious and very promising treatment protocol for patients with locally advanced LASCC or adeno/adenosquamous carcinoma of the uterine cervix.     

Comparison between conventional surgery and radiotherapy for FIGO stage I-II cervical carcinoma: a retrospective Japanese study

PURPOSE: To compare treatment outcome results of conventional surgery vs. radiotherapy (RT) for carcinoma of the uterine cervix. MATERIALS AND METHODS: A retrospective analysis was conducted of 152 patients with uterine cervical cancer radically treated with surgery or high dose-rate intracavitary brachytherapy (HDR-ICBT) with or without external RT from June 1991 to May 2004. The median follow-up time was 43.5 months (range, 1.0-130.0 months). The median age was 53 years (range, 25-81 years). There were 13 patients (9%) in stage IA, 52 (34%) in stage IB, 24 (16%) in stage IIA, and 63 (41%) in stage IIB. The conventional surgery group included 115 patients (76%) who underwent hysterectomy with pelvic lymph node dissection. Of these, 72 (63%) received postoperative radiotherapy. Thirty-seven patients (24%) were assigned to the RT group. Of these, 14 (38%) received chemoradiotherapy. Three patients with stage I received ICBT-alone without external beam irradiation. RESULTS: The 5-year cause-specific survival (CSS) rates for surgery and RT were 79.9% and 82.3%, respectively; the difference between these two treatments was not statistically significant (P = 0.8524). The differences in the survival rates between the two treatments for each of the stage I or stage II patients were also not statistically significant (P = 0.8407 for stage I and P = 0.6418 for stage II). CONCLUSIONS: This retrospective study suggests that RT results in compatible survival with conventional surgery for patients with stage I-II cervical carcinoma.     

Changes of Ki-67 index in squamous cell carcinoma of the cervix during the early course of radiotherapy and prediction of prognosis

PURPOSE: To determine whether changes in the Ki-67 index during the early course of radiotherapy could predict the prognosis in squamous cell carcinoma of the uterine cervix and be of value in clinical practice. MATERIALS AND METHODS: Biopsy specimens from 23 cases of histologically confirmed squamous cell carcinoma of the cervix were stained with anti-Ki-67 monoclonal antibody prior to radiotherapy and after 9 Gy. The correlation between the Ki-67 index, local control and distant metastasis was determined by Spearman's correlation test. RESULTS: Median age of the patients was 49. According to the FIGO staging system four patients had Stage IIA, 16 had Stage IIB, one had Stage IIIA and two had Stage IIIB disease. Among the whole group brachytherapy was applied to 17 patients (17/23) and weekly cisplatin (40 mg/m2) was applied to 15 patients (15/23). The mean Ki-67 index prior to radiotherapy and after 9 Gy for the entire group were 58.5% and 46.0%, respectively. The Ki-67 index after 9 Gy decreased in most of the patients (74%). During a median follow-up of 23 months four patients developed local recurrence and four patients developed distant metastasis. No significant correlation was detected among the local control and changes in Ki-67 index after 9 Gy, whereas there was a moderate correlation between distant metastasis and changes in Ki-67 index after 9 Gy (r = 0.51, p = 0.01). CONCLUSION: The Ki-67 index can be used safely as a proliferation marker in cervical carcinomas, and changes in the Ki-67 index during the early course of radiotherapy may predict the metastatic potential. However prospective studies including a large number of patients with long-term follow-up are necessary to confirm the clinical utility of this marker in cervical cancer.     

Umblical metastasis in cervical cancer

INTRODUCTION: Objective cutaneous metastasis from carcinoma of the uterine cervix is an uncommon occurrence. The outcome of patients with skin metastasis is usually poor as they are often associated with locoregional recurrence. This metastasis impairs the quality of life and shortens survival. Consequently, physicians should be aware of the possible existence of skin metastasis in cervical cancer. Clinical suspicion should lead to a careful additional evaluation whenever a cutaneous nodule presents in the course of the disease. CASE REPORT: We report a rare case of metastasis from squamous cell carcinoma of cervix to the umbilicus. The patient was diagnosed with stage IIB FIGO. Four months after chemoradiation patient presented with a nodule in the umbilical region. Biopsy performed and metastatic squamous cell carcinoma was diagnosed. Patient underwent salvage therapy with paclitaxel and carboplatin. CONCLUSION: To the best of our knowledge, this is a rare reported occurrence of umbilical metastasis in cervical cancer without prior laparotomy or laparoscopy. This metastatic lesion has a grave prognosis and the mean survival is about 3 months like our case.     

子宫颈鳞状细胞癌复发患者血清鳞状细胞癌抗原监测的意义

目的探讨血清鳞状细胞癌抗原（SCCAg）在监测宫颈鳞癌患者复发中的意义。方法对1999-2005年收治的72例宫颈鳞癌复发患者血清SCCAg水平与诊断、预后的关系进行单因素和多因素分析。结果72例复发患者中,术后复发30例、放化疗后复发42例,其中血清SCCAg水平升高者61例（占85％）。此61例患者中,20例在随诊中首先出现血清SCCAg水平升高而临床及影像学检查未发现肿瘤,血清SCCAg水平提前升高的中位时间为3个月,平均4．6个月（1～13个月）。72例复发患者中,45例患者无任何临床症状,仅因血清SCCAg水平升高或常规随诊发现复发;27例患者有症状,其中单侧下肢水肿或疼痛15例,阴道不规则流血7例,出现远处转移相关症状5例。细胞或组织病理学检查诊断复发者33例;临床及影像学检查结合血清SCCAg水平诊断复发者39例,其中29例仅依靠血清SCCAg水平升高及影像学检查即诊断复发。72例复发患者的中位生存时间为11个月,平均生存时间为23个月（2～62个月）,总的3年生存率为25％,5年生存率为19％。单因素分析发现,初治前患者血清SCCAg水平、病理分级、复发部位、复发后治疗方式以及复发时、复发后治疗中、治疗后血清SCCAg水平对患者的3年生存率有明显影响（P〈0．01）;但20例血清SCCAg水平提前出现升高的患者与52例血清SCCAg水平未提前升高的患者相比,3年生存率分别为22％、27％,差异无统计学意义（P=0．5761）。多因素分析发现,复发患者仅病理分级、复发后的治疗方式是独立的预后影响因素（P〈0．05）;而复发部位及各种血清SCCAg状态不是独立的预后影响因素（P〉0．05）。结论血清SCCAg水平监测在宫颈鳞癌复发患者中的诊断及其对预后的判断中有一定的价值。     

Dose-Tumor Response for Carcinoma of Cervix: An Analysis of 594 Patients Treated by Radiotherapy

This is a retrospective study of 594 histologically proven carcinomas of the uterine cervix treated with radiotherapy alone between January 1970 and December 1986. The age of this group of patients ranged from 22 to 86 years, and the median age was 57 years. There were 544 (91.6%) patients with squamous carcinoma and 36 (6.1%) with adenocarcinoma. There were 24 (4.0%) patients who were treated by two sessions of intracavitary brachytherapy only using intrauterine tandem and vaginal ovoids; 513 (86.4%) patients received whole pelvis irradiation followed by two sessions of brachytherapy at 1-week intervals, with or without additional boost to the parametrium. The dose to point A ranged from 40 to 100.9 Gy for the patients with stage IB to IIIB disease. The 5- and 10-year survival for stages IB, IIA, IIB, IIIA, and IIIB were 90.0, 82.1, 72.0, 50.0, 51.5, and 86.9, 71.0, 67.5, 41.7, and 46.9%, respectively. There was no long-term survivor for stage IV disease; the median survivals for patients with stages IVA and IVB were 15.2 and 9.3 months, respectively. Dose response was demonstrated for stages IIB and III tumors; dose to point A greater than 85 Gy was associated with better central control (P = 0.0036 and 0.0234, respectively). However, further increase in dose to point A beyond 85 Gy was not associated with improvement in central control (P = 0.3128 and 0.3394, respectively, for stages IIB and III). It was also found that the occurrences of rectosigmoid and bladder complications were correlated with the rectal and point A dose. Thus, for these patients, there is no need to increase the dose to point A beyond 85 Gy so that the risk of radiation sequelae can be cut down.     

Evaluation of gemcitabine in patients with squamous cell carcinoma of the cervix: a Phase II study of the gynecologic oncology group

PURPOSE: A multicenter Phase II trial was conducted to evaluate the activity and toxicity of gemcitabine in patients with previously treated squamous cell carcinoma of the uterine cervix. PATIENTS AND METHODS: Patients were required to have measurable disease with adequate performance status, bone marrow, hepatic, and renal function. Histologic confirmation of the primary diagnosis as squamous cell cancer of the uterine cervix was mandatory. Patients were allowed one prior chemotherapy regimen, usually cisplatin-based. The initial dose of gemcitabine was 800 mg/m(2) weekly times three with 1 week off until progressive disease or adverse effects prohibited further therapy. Doses were escalated or reduced based on previous cycle toxicity. RESULTS: Twenty-seven patients were entered into the trial. One patient never received the drug and 1 patient was inevaluable for response. A median of two cycles were administered to each patient (range: 1-7 cycles). The overall response rate (two partial responses) was 8% with 21% of patients having stable disease. The median progression-free interval was 1.9 months (range: 0.5-9.0) and overall survival was 4.9 months (range: 1.5-16.3). Two patients had grade 4 neutropenia; 1 patient had grade 4 anemia. The median WBC nadir in the 13 patients experiencing any leukopenia was 2300/microl (range: 400-3800). There was only one episode of grade 4 gastrointestinal toxicity. CONCLUSIONS: Gemcitabine as a single agent demonstrated minimal antitumor activity in previously treated patients with squamous cell cancer of the uterine cervix. Since gemcitabine in the dose and schedule employed is known to potentiate the cytotoxicity of cisplatin and radiotherapy (the current standard therapies for this disease), further development of gemcitabine would only be indicated in combination with these treatment modalities.     

A multi-institutional phase II trial of paclitaxel and carboplatin in the treatment of advanced or recurrent cervical cancer

Objective

The aim of this prospective trial was to evaluate the efficacy and safety of the combination of paclitaxel and carboplatin (TC) in patients with metastatic or recurrent cervical cancer.

Methods

This was a multicenter phase II trial of 3 weekly paclitaxel 175 mg/m² 3-hour iv day 1 followed by carboplatin AUC5 1-hour iv day 1 for maximum of 6 cycles until disease progression or prohibitive toxicity. Eligible patients had squamous or adenocarcinoma of the cervix with measurable stage IVB or recurrent, aged 20-75 years, Eastern Cooperative Oncology Group performance status 0-2, prior platinum-containing regimen 0-1, and no prior taxane. The primary endpoint was overall response rate (ORR) by RECIST.

Results

41 patients were enrolled, of which 39 were evaluable for analysis. 33 patients (84.6%) received prior radiotherapy. The confirmed ORR was 59% (95% CI, 43% to 75%); 5 patients (13%) achieved a complete response and median response duration was 5.2 months. The response rates for patients who had adenocarcinoma (n = 10) and prior platinum-based chemotherapy < 6 months (n = 7) were 40.0% and 0%, respectively. The median progression-free survival and overall survival times were 5.3 and 9.6 months, respectively. The most frequent grade 3 or 4 adverse events were neutropenia (79%), anemia (46%), thrombocytopenia (15%), and fatigue (8%). No treatment-related death was seen.

Conclusions

TC seemed to be feasible and effective similar to other cisplatin-based doublets for the treatment of metastatic or recurrent cervical cancer. Phase III trial is warranted to establish the clinical benefits of this combination.     

Adenosquamous carcinoma of the uterine cervix--adjuvant chemotherapeutic treatment with paclitaxel and carboplatin; a case report

Adenosquamous carcinoma of the uterine cervix is a rare mixture of malignant glandular and squamous epithelial elements. We present a case of a 56-year-old woman with Stage IV cervical carcinoma treated with paclitaxel and carboplatin chemotherapy after cytoreductive surgery. Solitary liver metastases were treated by ultrasound guided percutaneous sclerotherapy with 95% ethanol. For ten months the patient showed an objective response to the treatment with a good quality of life during that time. A year after the first, the second cytoreductive operation was performed and chemotherapy (paclitaxel, carboplatin, and epirubicin) followed. The patient died 20 months after establishing the diagnosis. Paclitaxel in combination with carboplatin as adjuvant chemotherapeutic treatment could be another promising agent for patients with advanced metastatic cervical adenocarcinoma.     

The importance of adjuvant chemotherapy and pelvic radiotherapy in high-risk early stage endometrial carcinoma

Objective

To determine the impact of a policy change in which women with high-risk early stage endometrioid endometrial cancer (EEC) received adjuvant chemoradiotherapy.

Methods

This is a population-based retrospective cohort study of British Columbia Cancer Registry patients diagnosed from 2008 to 2012 with high-risk early stage EEC, who received adjuvant chemoradiotherapy after primary surgery. High-risk early stage was defined as the presence of two or more high-risk uterine factors: grade 3 tumor, more than 50% myometrial invasion, and/or cervical stromal involvement. Adjuvant therapy consisted of 3 or 4 cycles of carboplatin and paclitaxel chemotherapy, followed by pelvic radiotherapy. Sites and rate of recurrence were compared to a historical cohort diagnosed from 2005 to 2008 in which none of the patients received adjuvant chemoradiotherapy. Five-year progression-free and overall survival rates were calculated.

Results

The study includes 55 patients. All patients except for 2 received at least 3 cycles of chemotherapy. All patients received pelvic radiotherapy except for 2 who received brachytherapy only. Median follow-up was 27 months (7–56 months). Four patients (7.3%) recurred, including three with distant recurrence only and one with both a pelvic and paraaortic nodal recurrence. The historical cohort had a 29.4% recurrence rate, and therefore the hazard ratio for recurrence was 0.27 (95% CI 0.02–4.11). Five-year progression-free and overall survival rates were 88.6% and 97.3%, respectively.

Conclusion

Patients with high-risk early stage endometrial carcinoma treated with adjuvant chemoradiotherapy have a low rate of recurrence compared to those not receiving such therapy.     

P63 and EGFR as prognostic predictors in stage IIB radiation-treated cervical squamous cell carcinoma

OBJECTIVES: The purpose of this study was to determine the relation between p63, p53-related gene, epidermal growth factor receptor (EGFR), and spontaneous apoptosis in relation to radiotherapy in patients with FIGO stage IIB cervical carcinoma, who had undergone radiation and concurrent chemotherapy, retrospectively. METHODS: Eighty-four patients with FIGO stage IIB squamous cell carcinoma (SCC) of the uterine cervix, who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996, were included in the present study. The clinicopathologic features, patterns of treatment failure, and survival data were compared with the expressions of p63 and EGFR, which were determined by immunohistochemistry and with apoptosis by TUNEL on tissue-arrayed slides. Univariate and multivariate analyses were performed to determine the prognostic factors that influence patient survival. RESULTS: Overall the indices of the expressions of p63 and EGFR in stage IIB cervical carcinoma were 18.7 and 26.6%, respectively, and these were found to be correlated. EGFR expression was significantly associated with extrapelvic failure (P = 0.03), whereas p63 was associated with locoregional failure (P = 0.03). The spontaneous apoptotic index showed no prognostic value, but the immunoreactivities of p63 and EGFR were associated with a worse prognosis by both univariate (P = 0.01 and 0.04, respectively) and multivariate analysis (95% CI:2.0-4.4, RR:3.2 and 95% CI:4.9-8.7, RR:6.7, respectively). CONCLUSIONS: The expression of p63 gene is associated with poor survival and locoregional failure, whereas EGFR expression was found to be a prognostic predictor of extrapelvic failure. Both molecules were found to be potent molecular risk factors in patients with FIGO stage IIB SCC of the uterine cervix, who had received radiotherapy and concurrent chemotherapy.     

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in uterine cervical cancer patients with high-risk factors

OBJECTIVES: To determine whether concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy is better than CCRT alone in the management of FIGO stage bulky IB and IIB uterine cervical cancer. METHODS: Two hundred and five FIGO stage bulky IB and IIB patients with squamous cell carcinoma of the uterine cervix treated with CCRT were divided into 2 groups: (1) CCRT alone (n=103, Group A) and (2) CCRT plus adjuvant chemotherapy (n=102, Group B), and treatment outcomes were retrospectively compared between the two patient groups. RESULTS: Only 63% of patients received all three planned cycles of adjuvant chemotherapy, while 16% received only one cycle because of increased treatment-related morbidity or other causes. There were no treatment-related deaths. Although 37 patients experienced failures after completion of treatment, no significant differences were found in patterns of local and regional failures between the two groups. The incidence of distant metastasis, including para-aortic or supraclavicular lymph node metastases, was not reduced in patients of Group B (8% in Group A vs. 7% in Group B). Overall five-year actuarial survival rates for Group A and Group B patients were 85% vs. 80%, and five-year disease-free survival rates were 83% vs. 78%, respectively. CONCLUSIONS: Our data failed to show discernable therapeutic advantage of adjuvant chemotherapy with given after CCRT for the management of FIGO stage bulky IB and IIB uterine cervical cancer patients. A future clinical trial will be necessary to test the clinical efficacy of the adjuvant treatment using newly developed agents in uterine cervical cancer patients.     

Combination chemotherapy of docetaxel and carboplatin in advanced or recurrent cervix cancer. A pilot study

OBJECTIVES: This is a pilot study for a future trial to assess the efficacy and safety of combination chemotherapy with docetaxel and carboplatin in advanced or recurrent uterine cervix cancer. METHODS: The patients eligible for this study had histologically confirmed, advanced (stage IB2-IV) or recurrent uterine cervix cancer. Eligible patients had measurable lesions and must have sufficient bone marrow, renal, and liver functions. Docetaxel was administered intravenously (IV) at 60 mg/m2 followed by IV carboplatin administration based on AUC = 6. Chemotherapy was repeated in 1-6 courses depending on the purpose of the therapy. The response was evaluated based on RECIST criteria. The toxicity grade was determined by NCI-CTC version 2. RESULTS: During January 2001 and April 2004, 17 patients were entered in this study. The distribution of stage was IB2, 3; IIB, 8; IIIB, 3; IVB, 1; recurrent, 2. There were 9 squamous cell carcinomas, 6 adenocarcinomas, 1 adenosquamous cell carcinoma, and 1 small cell carcinoma. The overall response rate was 76% (2 CR, 11 PR, and 4 SD). No progression of disease was observed. All 5 adenocarcinoma patients in the neoadjuvant chemotherapy group responded including 1 pathological CR. The incidences of grade 3/4 toxicities were 76% for neutrocytopenia, 12% for thrombocytopenia, and 6% for anemia. No grade 3/4 neurotoxicity was observed. CONCLUSIONS: The combination of docetaxel and carboplatin is an effective and safe treatment for uterine cervix cancer. Further evaluation particularly targeted on cervical adenocarcinoma is warranted.     

Concurrent carboplatin/5-FU and radiotherapy for locally advanced cervical carcinoma

Landoni F, Maneo A, Colombo A, Cormio G, Placa F, Nava S, Rossi R,Mangioni C. Concurrent carboplatin/5-FU and radiotherapy for locally advancedcervical carcinoma. Int J Gynecol Cancer 1997; 7 :471–476.
Despite innovative techniques in radiotherapy delivery no significant improvement in survival rates for cervical carcinoma has been achieved during the last few decades. Concurrent chemoradiation (CR) is one of the several avenues being explored to improve these results.
Forty-seven women with locally advanced (IB2-IVA) squamous cell carcinoma of the uterine cervix were treated with CR, comprising a combination of external and intracavitary radiation along with three cycles of 5-FU and carboplatin.
Treatment was well tolerated with 81% of the patients completing the CR protocol as planned. Acute toxicity was severe but manageable: 16 patients (34%) experienced grade 3–4 acute toxicity. Late morbidity occurred in 15% of the patients. Overall response rate was 88%. At a median follow-up time of 19 months (range 12–59) 62% of the patients are alive without disease and 18% are dead of disease. Actuarial two-year survival rate for the whole group of patients is 64%.
Concomitant carboplatin/5-FU and radiotherapy is a safe and tolerable mean of treatment for locally advanced cervical cancer. The true advantage for survival, however, can be demonstrated only after completion of randomized trials comparing CR with conventional radiation therapy.     

First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cancer of the cervix--a phase II study

OBJECTIVE: The aim of this study was to assess the role of first-line chemotherapy with paclitaxel and platinum in the treatment of advanced or recurrent cervix cancer. METHODS: Twenty patients with advanced or recurrent cancer of the cervix with no prior chemotherapy and measurable disease were entered in a phase II trial from September 1995 to September 1998. Seventeen patients were treated with paclitaxel at 135 mg/m(2) over 24 h followed by cisplatin at 75 mg/m(2) every 4 weeks. Three patients with impaired renal function were treated with paclitaxel at 135 mg/m(2) over 3 h with carboplatin at 300 mg/m(2). RESULTS: A clinical response rate of 45% was noted (two complete responses and seven partial responses) with a median duration of 6 months (range: 1.5-9). The median progression-free interval and overall survival in patients with a clinical response was 10.5 and 13 months, respectively, compared to 4 (P = 0.015) and 6 months in the nonresponders (P = 0. 14). Seven of nine patients (77.8%) with a clinical response are alive. Patients with recurrences outside the radiation field had twice the response rate (60%) than that of those within the radiated field. The chemotherapy was well tolerated; the most significant toxicity was grade 3/4 neutropenia (55%). No patient had discontinuation of chemotherapy due to toxicity. CONCLUSIONS: First-line chemotherapy with paclitaxel and platinum for advanced and recurrent cervix cancer is promising and deserves consideration for large phase III trials.     

Comparison of clinical outcomes of adenocarcinoma and adenosquamous carcinoma in uterine cervical cancer patients receiving surgical resection followed by radiotherapy: A multicenter retrospective study (KROG 13-10)

Objective

To evaluate the prognostic influence of adenocarcinoma (AC) and adenosquamous carcinoma (ASC) in patients with FIGO stage IB–IIA cervical cancer who received radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT).

Methods

We analyzed 1323 patients who satisfied the following criteria: histologically proven squamous cell carcinoma (SCC), AC, or ASC of the uterine cervix; FIGO stage IB–IIA disease; no history of neoadjuvant chemotherapy; and a history of radical hysterectomy with pelvic lymph node (PLN) dissection, followed by postoperative pelvic RT at a dose ≥ 45 Gy. The median age was 50 years. Median RT dose delivered to the whole pelvis was 50.4 Gy, and 219 (16.6%) patients received brachytherapy at a median dose of 24 Gy. Concurrent chemotherapy was delivered to 492 (37.2%) patients.

Results

Pathologic risk factors were not different according to pathologic subtype. The median follow-up duration was 75.7 months. Locoregional recurrence-free survival, relapse-free survival (RFS), and overall survival were significantly affected by histology, tumor size, PLN metastasis, parametrial invasion, lymphovascular invasion, and deep stromal invasion. The 5-year RFS rates were 83.7%, 66.5%, and 79.6% in patients with SCC, AC, and ASC histology, respectively (P < 0.0001). By multivariate analysis, AC histology was the only significant prognostic factor affecting all survival outcomes.

Conclusions

AC histology was associated with poor survival outcomes in patients with FIGO stage IB–IIA cervical cancer who received adjuvant RT or CCRT. Prognosis of ASC histology was closer to that of SCC histology than that of AC histology.     

Phase II study of paclitaxel in combination with carboplatin for patients with recurrent or persistent uterine sarcoma

Objective

To evaluate the efficacy and toxicity of combined paclitaxel and carboplatin treatment for persistent or recurrent uterine sarcoma.

Methods

Paclitaxel was administrated at 175?mg/m² intravenously over 3?h plus carboplatin at AUC 5 intravenously over 30?min every 3-week cycle in patients with recurrent or progressive uterine sarcoma, who were unsuitable candidates for curative treatment with either surgery or radiotherapy. The Simon’s two-stage optimal design was chosen for defining the total number of patients required for the phase II study. A total of 13 patients were entered in the study at the first stage of trial. A median of four cycles were administrated per patient, with a range of one to nine cycles. Prior to the study, 4 (30.8?%) of the 13 patients had received radiotherapy or chemotherapy. The response was measured by evaluation of the size of the mass by CT scan.

Results

The overall response rate was 15.4?% (2/13), with two patients exhibiting partial responses. There was 1 (7.7?%) case of stable disease and 9 (69.2?%) cases of progression disease. The median progression free survival was 2.23?months (95?% confidence interval 1.94–3.67). Peripheral neuropathy and hematologic toxicity, including anemia and neutropenia, were the most frequent adverse events. One patient died from treatment-related toxicities.

Conclusions

Paclitaxel in combination with carboplatin demonstrated acceptable levels of toxicity, but it was not active in the treatment of recurrent or progressive uterine sarcoma. This regimen might have limited role for advanced uterine sarcomas.