Mitoxantrone in the treatment of advanced non-squamous carcinoma of the cervix (A phase II trial of the gynecologic oncology group)

Twenty-five evaluable patients with advanced non-squamous carcinoma of the uterine cervix were treated with mitoxantrone 12 mg/m² every three weeks. All patients had good performance status and measurable disease and only 11 had received prior chemotherapy. One complete and one partial response were noted among 15 patients with no prior chemotherapy while no responses were seen in 11 previously treated patients. The major toxicity was myelosuppression; other toxicity was mild. The median progression-free interval was 2.1 months and median survival 4.3 months. Mitoxantrone displays minimal activity in patients with advanced non-squamous carcinoma of the cervix.     

A case of glassy cell carcinoma of the uterine cervix that responded to neoadjuvant chemotherapy with paclitaxel and carboplatin

Glassy cell carcinoma of the uterine cervix is a rare tumor, and has a poor prognosis because of its aggressive clinical behavior and resistance to radiotherapy and chemotherapy. We report a case of bulky glassy cell carcinoma of the uterine cervix that effectively responded to paclitaxel and carboplatin in a neoadjuvant setting. The patient was a 30-year-old woman who became aware of vaginal bleeding and was referred to our hospital because of a cancerous tumor of the uterine cervix. Physical examination showed the cervical tumor to be approximately 8 cm in diameter with no involvement of the parametrium or vagina. The biopsy results suggested a diagnosis of glassy cell carcinoma. The final diagnosis was glassy cell carcinoma of the uterine cervix, stage 1b2. Neoadjuvant chemotherapy with paclitaxel and carboplatin was administered for downstaging. The response rate was 67.9% (partial response) under magnetic resonance imaging, and elevated serum cancer-related antigen 125 (119 U/ml) and squamous cancer cell antigen (34 ng/ml) were reduced to 34 U/ml and 3.3 ng/ml, respectively. Following neoadjuvant chemotherapy, she underwent radical hysterectomy and adjuvant chemotherapy with the same regimen. The clinical course was very good. We speculate that glassy cell carcinoma is a sensitive tumor to paclitaxel and carboplatin. Further evaluation concerning diagnosis and treatment, however, is needed to improve the prognosis of patients with glassy cell carcinoma.     

A phase II trial of gallium nitrate (NSC #15200) in advanced or recurrent squamous cell carcinoma of the cervix

Twenty-four evaluable patients with advanced, persistent or recurrent squamous cell carcinoma of the cervix were treated with 750 mg/m² of gallium nitrate (NCS # 15200) every three weeks. No patient had prior cytotoxic chemotherapy. Two patients had a partial response (8.3%), ten patients had stable disease (41.7%), and twelve (50%) had increasing disease. The 95% upper confidence bound for response is 24.0%. The major toxicities were nausea, vomiting and anemia. Gallium nitrate has minimal activity in patients with previously untreated squamous cell carcinoma of the cervix.Address for offprints: GOG Administrative Office, Suite 1945, 1234 Market Street, Philadelphia, PA 19107, USAThe following are participating institutions: University of Alabama at Birmingham (CA 12484), The Oregon Health Sciences Center University*, University of California Medical Center at Los Angeles (CA 13630), University of North Carolina School of Medicine (CA 23073), Bowman Gray School of Medicine of Wake Forest University (CA 21946), The Albany Medical College of Union University (CA 27469), University of Pittsburgh School of Medicine*, Eastern Virginia Medical School (CA 40296), State University of New York at Stony Brook* and Pennsylvania Hospital*. * = Unfunded     

宫颈癌经腔内微波热疗联合放疗后的病理及肿瘤抗原改变

目的 探讨热放疗对宫颈癌病理组织学及鳞状上皮细胞癌相关抗原(squamous cell carcinoma antigen,SCC)的改变.方法 将Ⅰb期宫颈鳞癌患者66例随机分为两组.实验组32例在常规的腔内放疗的基础上同期增加宫颈腔内微波热疗,2周后行官颈癌根治术;对照组34例接受常规的腔内放疗,2周后行根治术.比较两组术后病理组织学及SCC改变.结果 1、实验组癌细胞出现中重度放疗反应为87.50％,优于对照组的61.76％(P＜0.05);实验组癌周炎症细胞中重度反应为84.37％,优于对照组的55.88％(P＜0.05);实验组癌周纤维组织中重度反应为75.00％,优于对照组的50.00％(P＜0.05).2、实验组SCC降低率为87.50％,高于对照组的52.94％(P＜0.05).结论 1、官颈癌术前放热疗能增强放疗对癌细胞的杀伤作用,加重癌周炎性细胞及纤维细胞反应.2、官颈癌热放疗能较单纯放疗有效降低SCC水平.     

尼妥珠单抗联合放化疗治疗Ⅲ、ⅣA期鼻咽癌的临床研究

目的 探讨三维适形放疗(3D-CRT)联合尼妥珠单抗及紫杉醇顺铂化疗方案治疗Ⅲ、ⅣA期鼻咽癌的疗效及毒副作用.方法 经组织病理确诊的Ⅲ、ⅣA期(2008分期)鼻咽癌初诊患者60例.采取3D-CRT及同期和序贯紫杉酵顺铂方案化疗,每周一放疗前行尼妥珠单抗100 mg治疗,共6～7次.观察2个月后原发灶CR率、颈部淋巴结CR率、治疗后1、2、3年局部控制率及无远处转移率及不良反应情况.结果 放疗后2个月原发灶CR率为98.3％、颈部淋巴结CR率96.7％.治疗后1年局部控制率为100％、无远处转移率为96.7％;2、3年后局部控制率、无远处转移生存率均为100.0％.主要不良反应为放射性咽喉炎、放射性皮炎和恶心呕吐、白细胞减少、疲乏等.结论 尼妥珠单抗联合3D-CRT及紫杉醇及顺铂同期及序贯化疗治疗局部晚期鼻咽癌完全缓解率及局部控制率、无远处转移生存率提高,耐受性好.     

168例子宫内膜癌淋巴结转移规律的研究

目的 探讨子宫内膜癌扩散至盆腔和腹主动脉旁淋巴结的途径。方法对接受全子宫和盆腔淋巴结切除术的168例子宫内膜癌患者,准确记录肿瘤所处子宫腔位置、子宫肌层浸润深度、分期、病理类型、细胞学分级及切除淋巴结位置及阳性淋巴结数,并进行相关分析。结果肿瘤位于宫底部、宫体部、累及宫颈者子宫内膜癌淋巴结转移率分别是19．2％、20．6％、37．5％,均以髂外淋巴结转移为最常见。病灶局限于宫底、宫体部者多为髂外、闭孔淋巴结转移;累及宫颈者以髂外、髂总淋巴结转移为常见。前者髂总淋巴结转移率为30．8％,后者为66．7％,P〈0．01。所有腹主动脉旁淋巴结阳性和累及宫颈者的髂总淋巴结均为阳性,而病灶限于宫体的腹主动脉旁淋巴结转移者仅有27％髂总淋巴结阳性。肌层浸润程度、病理类型及细胞分化程度与盆腔淋巴结转移密切相关。结论位于宫体部的肿瘤可直接或由宫颈转移至髂外淋巴结,宫颈受累者最易发生髂总和髂外淋巴结转移。病灶累及宫颈者髂总淋巴结可作为腹主动脉旁淋巴结的前哨淋巴结。     

A Phase II study of carboplatin in advanced squamous cell carcinoma of the cervix (a Gynecologic Oncology Group study)

Summary The Gynecologic Oncology Group conducted a Phase II trial of carboplatin in patients with measurable advanced squamous cell carcinoma of cervix. No prior therapy with cytotoxic drugs was permitted in patients entered into this study. Patients entered were GOG performance status 2 or better.Carboplatin 400 mg/m² (340 mg/m² in patients who had had prior pelvic radiotherapy with subsequent escalation to 400 mg/m² if bone marrow tolerance was good) was administered as a 15-minute IV infusion. Treatments were repeated every four weeks until disease progressed or until toxicity prohibited further therapy.Thirty-nine evaluable patients were treated. Two complete and nine partial responses were observed (response rate 28.2%). No neurotoxicity and only mild reversible nephrotoxicity was seen. Gastrointestinal toxicity was severe in three patients (7.7%). Dose limiting toxicity was myelosuppression.Carboplatin is active against squamous cell carcinoma of cervix and appears to be less nephrotoxic, neurotoxic, and nauseogenic than cisplatin. Randomized studies of this drug against cisplatin are indicated to determine the role of carboplatin in the therapy of squamous cell carcinoma of cervix. Address for offprints: GOG Headquarters, Suite 1945, 1234 Market Street, Philadelphia, PA 19107.     

XRCC1基因多态性与宫颈鳞癌放疗敏感性的关系

【摘要】目的 探讨XRCC1基因Arg194Trp、Arg399Gln单核苷酸多态性（SNP）与外生型宫颈鳞状细胞癌放疗敏感性的关系。方法 采用错配扩增聚合酶链式反应（MAMA-PCR）方法检测73例外生型宫颈鳞状细胞癌患者血液标本的XRCC1 Arg194Trp、Arg399Gln两个SNP的基因型频率分布,进一步分析其与宫颈癌放疗敏感性的关系。结果 XRCC1基因Arg194Trp、Arg399Gln基因型完全缓解组和部分缓解组分布情况均无统计学差异（P>0.05）。结论XRCC1基因Arg194Trp、Arg399Gln SNP与外生型宫颈鳞状细胞癌放疗敏感性无相关性。     

Oncoprotein c-erbB-2 in squamous cell carcinoma of the uterine cervix and evaluation of its significance in response of disease to treatment

Tissues from 50 cases of squamous cell carcinoma of the uterine cervix were analysed for immunohistochemical expression of c-erbB-2 oncoprotein and the patients were followed-up for 2 years. Immunopositivity of c-erbB-2 was studied with reference to clinical stage, histopathological differentiation and response to the cancer therapy. Expression of c-erbB-2 protein was found to be higher (37.5%) in cases with stage II disease, whereas more expressions were noticed in poorly differentiated squamous cell carcinoma (33.3%). Among cases who showed complete response to the treatment, 20.8% were positive for c-erbB-2 oncoprotein. On the contrary, 36.8% of prognostically unfavourable cases revealed positivity for c-erbB-2 immunostaining. However, the difference between c-erbB-2 expressions of these two said groups of patients, which were divided in accordance with the response to treatment, did not attain to statistical significance. Study on c-erbB-2 among larger number of patients with cervical carcinoma may prove to be an important factor in response to cancer therapy.     

Phase II study of ifosfamide and mesna in patients with previously-treated carcinoma of the cervix

Summary Thirty patients with advanced squamous carcinoma of the uterine cervix recurrent after radiotherapy or surgery and refractory to first-line chemotherapeutic agents were treated with ifosfamide in a dose of 1.2 grams/m² IV daily for five days every four weeks and Mesna 300 mg/m² IV every four hours for three doses daily for five days. One patient had an inadequate trial and two were inevaluable for response, leaving 27 patients evaluable for response. All but two patients had received prior radiotherapy and all but one prior cisplatin-based or cisplatin analog chemotherapy. Seventeen patients had prior surgery. All patients were Gynecologic Oncology Group performance status 0, 1, or 2. Partial responses were observed in three patients (11.1%), two with pelvic and one with extrapelvic disease. A 90% confidence interval for the true response rate is 4.5%–24.8%. Severe (grade 3 or 4) leukopenia and anemia were seen in nine and seven patients, respectively. Severe thrombocytopenia was not observed. Three patients had grade 3 or 4 neurotoxicity, and one had grade 3 renal impairment. Reversible alopecia was universal. This dose and schedule of ifosfamide and Mesna is active in patients with squamous carcinoma of the cervix failing platinum-based therapy. Phase II testing in untreated patients is currently underway.     

自制电子束限光筒对宫颈癌局部病灶的治疗效果

目的评价使用自制电子束限光筒消除治疗宫颈癌局部病灶的疗效。方法阴道电子束限光筒采用有机玻璃筒制作。经阴道置于病变部位,限光筒后端经一识配装置连接直线加速器。36例宫颈癌患者,中位年龄51岁。Ⅰb～Ⅱb期23例,术后复发13例。放疗前阴道镜检查肿瘤平均直径4cm。使用10mV电子线能量,300cGy/次,1次/d治疗,5次/周。治疗总量1500～3000cGy。电子束经阴道限光筒治疗完成后,行盆腔野常规外照射结合腔内192铱后装近距离放疗。结果31例宫颈癌消除治疗后阴道镜复查,有效率达86.11%,局部肿瘤消退明显,暴露出宫颈口,可顺利的进行后装腔内近距离治疗。结论经阴道电子束限光筒治疗,Ⅰb、Ⅱb期宫颈癌能明显改善局部症状并为进一步治疗创造更佳时机,也是一种行之有效的根治性放射治疗手段。     

A phase II clinical trial of diaziquone (AZQ) in the treatment of patients with recurrent adenocarcinoma and adenosquamous carcinoma of the cervix

Summary Twenty-six patients with recurrent adenocarcinoma and adenosquamous carcinoma of the uterine cervix were treated with diaziquone (AZQ) 22.5 mg/m² diluted in 150 ml normal saline every three weeks. In the absence of adverse effects the second dose and all subsequent doses were escalated to 30 mg/m². All patients had measurable disease and only 11 had received prior chemotherapy. Two partial responses were noted among 15 patients with no prior chemotherapy, while no responses were observed among 11 previously treated patients. The major toxicity was leukopenia and thrombocytopenia. Median progression-free interval was 1.5 months and median survival was 4 months. AZQ displays minimal activity against recurrent nonsquamous carcinoma of the cervix at the dose and schedule used.     

A Phase II study of CHIP in advanced squamous cell carcinoma of the cervix (a Gynecologic Oncology Group study)

Summary The Gynecologic Oncology Group (GOG) conducted a Phase II trial of CHIP, cis-dichloro-trance-dihydroxybis-(isopropylamine)-platinum IV, in patients with measurable advanced squamous cell carcinoma of the cervix. No prior therapy with cytotoxic drugs was permitted in patients entered into this trial. All patients had a GOG performance status of 2 or better.CHIP at a starting dose of 230 mg/m² was administered as a 30-minute IV infusion. Dose escalation was permitted to a maximum of 300 mg/m². Treatments were repeated every four weeks until disease progressed or until toxicity prohibited further therapy.Thirty-six evaluable patients were entered between January and July, 1984. Of these, 34 were evaluable for response. Four complete and three partial responses were observed (response rate 20.6%). No neurotoxicity was noted and only mild and reversible nephrotoxicity was reported. Grade 3 gastrointestinal toxicity was reported in twenty patients (56%). Dose-limiting toxicity was myelosuppression.CHIP is an active agent against squamous cell carcinoma of the cervix and appears to be less neurotoxic and nephrotoxic than cisplatin. Gastrointestinal toxicity was moderate and appears equal to that seen with cisplatin at a dose of 50 mg/m² given as a rapid IV infusion and more toxic than an equivalent dose of cisplatin administered over 24 hours. Randomized studies comparing CHIP and cisplatin are indicated to better define the relative therapeutic indices of these two compounds in the treatment of advanced squamous carcinoma of the cervix. Address for offprints: GOG Headquarters, Suite 1945, 1234 Market Street, Philadelphia, PA 19107.     

Results of treatment of cancer of the cervix in Wellington: 1975-9

A review was undertaken of all patients treated for invasive carcinoma of the cervix in the Wellington region in the period 1975 to 1979. A total of 84 patients were assessed for the results and complications of treatment. Forty-one were stage I, 18 stage II, 18 stage III, and seven stage IV (FIGO staging). Treatment by different combinations of surgery and radiotherapy for each stage are described. Actuarial survival at five years is 54% for all stages. For stage I it is 86%, stage II 54%, and stage III 44%. There were only seven patients in stage IV. Seven patients (8.3%) suffered major complications, mainly gastrointestinal or genitourinary. Most complications occurred in patients treated with a combination of radical surgery followed by high dose external radiotherapy. This treatment should be reserved for selected patients who can be identified as having a very high risk of recurrence in the pelvis after surgery. Invasive cancer of the cervix is a highly treatable disease, with over half the patients surviving free of disease at five years, but screening programmes for early detection are essential.     

FMNL2在宫颈鳞癌组织中的表达及临床意义

目的探讨宫颈鳞癌组织中形成素2（FMNL2）的表达及临床意义。方法 2009年1月至2011年12月采用免疫组织化学方法检测FMNL2在30份正常宫颈组织和73份宫颈鳞癌组织中的表达情况,分析其与各临床病理参数的关系。结果 FMNL2在宫颈正常组织鳞状上皮中的表达率为6.67%（2/30）,在宫颈鳞癌组织中的表达率为67.12%（49/73）,二者比较,差异有统计学意义（χ2=31.088,P=0.000）;FMNL2在宫颈鳞癌组织中的表达与淋巴结转移有关（χ2=5.330,P=0.024）,与患者年龄、肿瘤分化程度、肿块大小、临床分期等无关（P〉0.05）。结论 FMNL2在宫颈鳞癌的发生、发展和转移中起着一定作用。     

FHIT蛋白在宫颈癌中的表达及临床意义

为探讨 FHIT的表达与宫颈癌临床病理指标及预后之间的关系 ,应用免疫组化方法检测 5 0例宫颈癌和 2 0例正常宫颈组织中 FHIT蛋白的表达。结果显示 ,5 0例宫颈癌中 ,2 7例显示 FHIT蛋白表达降低或缺失 ,FHIT表达的降低或缺失与肿瘤的组织学分级 (P=0 .0 0 2 )和淋巴结转移 (P=0 .0 16)明显相关 ;FHIT表达阳性者和阴性者的 3年生存率分别为 83 .3 %和 5 2 .2 % ,差异有显著性 (P=0 .0 3 7)。     

Phase II evaluation of dianhydrogalactitol in the treatment of advanced non-squamous cervical carcinoma

Summary In an on-going Phase II evaluation, dianhydrogalactitol (NSC 132313) was administered intravenously to 28 patients with advanced or recurrent non-squamous cell carcinoma of the cervix. The initial dosage was 60 mg/m²/wk with escalation to 75 mg/m²/wk if there were no adverse effects. Twenty-seven patients were evaluable for toxicity and response. There was one complete response and one partial response. Adverse effects were not infrequent but tolerable.     

在宫颈癌根治术中腹膜阴道延长的效果评价

目的探讨腹膜阴道延长术在宫颈癌手术中的意义。方法2001-01～2006-06笔者选择45岁以下宫颈癌患者14例,实施宫颈癌根治术后采用腹膜阴道延长术为研究组;取同期常规宫颈癌根治16例为对照组,比较两组术中及术后情况。结果两组在手术时间、术中出血量、术后恢复时间及并发症等方面均无显著性差异,而术后1个月测定阴道长度,术后6～12个月进行性生活满意度调查,两组有显著性差异(P<0.05),且研究组男女对性生活的满意度均高于对照组。结论在宫颈癌根治术中,采用腹膜阴道延长术,既不增加手术难度,又能延长阴道长度,有效改善患者术后生存质量,具有较高的临床应用价值。     

A Phase II Trial of Pyrazoloacridine (PZA) in Squamous Carcinoma of the Cervix – A Gynecologic Oncology Group Study

Purpose: The Gynecologic Oncology Groupperformed a Phase II study to determine the response rate ofPyrazoloacridine (PZA) in patients with advanced, persistentor recurrent squamous carcinoma of the cervix.Methods: PZA was administered at a dose of 750mg/m² intravenously over three hours every threeweeks. Results: Among 21 evaluable patients, therewere no complete and one (4.2%) partial response. Themajor toxicities were hematologic. Conclusion: PZA atthe dose and schedule employed has insignificant activity inthis population.     

Phase II study of esorubicin (4′-deoxydoxorubicin) in advanced or metastatic squamous carcinoma of the uterine cervix: A Gynecologic Oncology Group study

Summary Twenty-eight patients with advanced, measurable squamous carcinoma of the uterine cervix were treated with 62 courses of esorubicin at doses ranging from 20–35 mg/m² every three weeks. All patients were evaluable for response and toxicity. All patients had received prior therapy including radiation therapy in 28, chemotherapy in 23, and surgery in 11. All patients were Gynecologic Oncology Group (GOG) performance status 0, 1 or 2. There were no responses seen. Severe (grade 3 or 4) leukopenia, thrombocytopenia, and anemia were seen in 13, 3, and 9 patients, respectively. Gastrointestinal toxicity as well as alopecia were the other adverse effects. Mucositis and phlebitis were not seen. Neither clinical congestive cardiomyopathy nor decrement in left ventricular ejection fraction was observed. Lack of response in association with moderate toxicity using this dose and schedule of esorubicin in squamous carcinoma of the cervix previously treated with chemotherapy makes further study as a salvage agent unwarranted. Address for offprints: GOG Headquarters, Suite 1945, 1234 Market Street, Philadelphia, PA 19107, USA.