Assessment of bleomycin, adriamycin and mitomycin-C in the treatment of recurrent cervical cancer

Twenty women with recurrent squamous cell carcinoma of the cervix were treated with bleomycin followed by adriamycin and mitomycin-C. Treatment was repeated every 28 days. In 18 patients who could be assessed there was one complete response and five partial responses (response rate 33%). Two partial responses were seen in 13 lesions arising from previously irradiated sites of disease (response rate 23%). Three complete responses and three partial responses were observed in 10 lesions arising from non-previously irradiated sites of disease (response rate 60%). In all responding cases tumour regression was noted before the end of the third cycle of treatment. Toxicity was predictable and manageable. These results suggest that chemotherapy may be used as a cytoreductive procedure before radical local treatment.     

Treatment of advanced or recurrent cervical cancer by a new BOMP regimen consisting of bleomycin, vincristine, mitomycin-C, and low-dose consecutive cisplatin]

Twenty-five patients with cervical cancer (4 post-operative cases with FIGO stage Ib or IIb, 2 with stage IV, and 19 recurrence) were treated with a new BOMP consisting of bleomycin (5 mg/body, drip, i.v., days 1-7), vincristine (0.7 mg/m2, bolus, i.v., day 7), mitomycin-5 (7 mg/m2, bolus, i.v., day 7) and cisplatin (10 mg/m2, drip, i.v., days 1-7). The mean age of the patients was 54 years (range 30-77). Prior therapy included radiotherapy (13 cases), radical hysterectomy (11), and none (1). Fifteen (79%) of the 19 evaluable patients responded, including 6 with a complete response (CR) lasting over 15 months. Almost all the disease located in lung, liver, bone, and vulva showed a response. In particular, lesions confined to the lung had a 100% CR when the size of each tumor was under 2 cm in diameter even in the case of multiple metastasis. In contrast, 9 patients with pelvic disease had a 56% response with only 1 CR who had no previous radiotherapy. Such a poor response in the pelvic disease was considered to be due to vascularity reduced by prior radiotherapy. The important factors affecting the response to a new BOMP were found to be lesion size, prior radiotherapy, and the site of lesion. Patient age, performance status (PS), and the interval from a previous treatment to BOMP were not of significance with regard to response. The dose limiting factor was hematologic toxicities. Other toxicities including nausea, renal dysfunction, pulmonary fibrosis, and loss of hair were acceptable. Thus, the decrease in the PS of patients due to BOMP was minimal. It is suggested that this regimen will be useful as a neoadjuvant chemotherapy for advanced cervical cancer.     

Cyclophosphamide,adriamycin, and platinum chemotherapy in treatment of advanced and recurrent cervical carcinoma

The chemotherapeutic combination of cyclophosphamide, doxorubicin (Adriamycin), and cis-dichlorodiammineplatinum was used in the treatment of women with metastatic or recurrent cervical carcinomas not amenable to surgery or radiotherapy. A total of 20 patients with evaluable parameters were treated. Three partial remissions and one complete remission were obtained, giving an overall response rate of 20%.     

Combination cyclophosphamide, adriamycin, and cis-platinum in recurrent and metastatic cervical carcinoma

Thirty evaluable patients with recurrent and/or metastatic cervical cancer were treated with a combination of cyclophosphamide, adriamycin, and cis-platinum. We observed no complete response and three partial responses (10%). One year survival rate was 45%. CAP combination did not prove to be more effective than single agent cis-platinum.     

Cis-platinum, doxorubicin, and methotrexate treatment for recurrent cervical cancer

A combination of cis-platinum, doxorubicin (Adriamycin), and methotrexate was used to treat 28 patients with recurrent cervical cancer. Seven patients achieved a partial response with a median duration of ten months. Two patients achieved a complete response with a median duration of 14 months. The overall response rate was 32%. Ten patients with stable disease had a median progression-free interval of 4.5 months. Toxicity was acceptable.     

A phase II evaluation of cisplatin, bleomycin, and mitomycin-C in patients with recurrent squamous cell carcinoma of the cervix.

Cisplatin, bleomycin, and mitomycin-C were used to treat 25 patients with recurrent squamous cell carcinoma of the cervix. Six patients had a partial response, yielding a total response rate of 27%. Nine patients had stable disease. The median survival for the whole group was 30 weeks. The median survival for responders was 32 weeks. The median progression free interval for the whole group was 12 weeks and the median progression-free free interval for responders was 14 weeks. The toxicities noted were primarily nausea, vomiting, and myelosuppression. The combination of cisplatin, bleomycin, and mitomycin-C has modest effectiveness in the treatment of recurrent squamous cell carcinoma of the cervix, but represents no improvement over single-agent chemotherapy.     

宫颈癌复发后的手术治疗

尽管宫颈癌复发的治疗策略有诸多争议,但手术依然是延长晚期患者生命、甚至有机会根治肿瘤的重要手段之一。文章将依据既往放疗与否和病灶位置对宫颈癌复发分类,并阐述不同类型宫颈癌复发后的手术适应证,同时将重点介绍盆腔器官清除术对于放疗后盆腔局部复发的治疗作用。     

Ifosfamide, adriamycin and cisplatin (IAP) plus bleomycin (B) combination chemotherapy in patients with recurrent cancer of the uterine cervix

A combination chemotherapy of ifosfamide, adriamycin and cisplatin (IAP) plus bleomycin (IAP plus B) was used to treat nine patients with recurrent cervical cancer of the uterus. All patients had received conventional radiation therapy with or without hydroxyurea as a potential radiation sensitizer, and seven of them had measurable disease in a previous irradiated field (4 cases) or distant area (3 cases). The tumors included 5 squamous cell carcinomas (non keratinizing: 2, keratinizing: 3), two adenosquamous (including one glassy cell carcinoma), one adenocarcinoma (endometrioid type) and one argyrophil cell carcinoma. All histologic type cancers except argyrophil cell carcinoma responded to IAP plus B treatment. In seven evaluable cases, three complete responses (CR) and 3 partial responses (PR) were recorded (response rate was 85.7%), including 3 responded tumors within previously irradiated pelvic tissue. The median duration of CR was over 7 months and that of PR was 3.5 months. Side effects of IAP plus B were severe in hematologic toxicity (100% of grade 4 leucopenia) but acceptable, permitting five courses of treatments at four week intervals. The results obtained were encouraging, although therapeutic benefits of IAP plus B were not evident in a patient with argyrophil cell carcinoma and the intractable nature of this histologic type cancer in the uterine cervix was again emphasized.     

盆腔器官廓清术在复发宫颈癌治疗中的价值

盆腔器官廓清术（盆廓术）为中央型盆腔复发的宫颈癌患者提供了再次治愈的机会。姑息性盆廓术对部分周围型复发患者也可以起到减轻症状和改善生活质量的作用。满意的手术切缘是影响盆廓术疗效和患者预后的最重要因素。术前需要根据患者的临床表现、妇科检查、影像学检查进行重点评估,并综合患者既往治疗情况、一般机体状态、患者心理、术中探查情况等综合考虑,筛选合适病例,并选择合理的手术方式和入路,才能使复发宫颈癌患者从盆廓术中获益。     

Mitomycin C, vincristine, and bleomycin therapy for advanced cervical cancer.

The Southwest Oncology Group has treated 130 patients with advanced disseminated uterine cervical carcinoma no longer amenable to therapy with further radiation or surgery. Patients received one of three different schedules of mitomycin C, vincristine and bleomycin. A twice weekly schedule of bleomycin and vincristine produced response in 60% of patients. An infusion bleomycin schedule produced response in 39% of patients and a once weekly vincristine bleomycin schedule produced a 25% response rate (45% overall). Responding patients lived significantly longer than nonresponders (30 vs 18 weeks). Toxicities encountered included leukopenia, thrombocytopenia, peripheral neuropathy, gastrointestinal upset, dermatitis, and alopecia. We believe two of the schedules utilized represent an improvement in producing tumor remission induction in this previously recognized refractory carcinoma.     

Treatment of advanced cervical cancer by a combination of peplomycin, vincristine, mitomycin-C, and cisplatin

Eighteen patients with advanced or recurrent carcinoma of the cervix were treated with a combination of peplomycin, vincristine, mitomycin-C, and cisplatin (POMP). Ten of the 16 evaluable patients (63%) responded, including 4 with a complete response. Median duration of the response was 7 months. Two of 6 with intrapelvic recurrent tumors responded to some extent following intraarterial infusion. The subcutaneous infusion of peplomycin was well accepted by the patients. Toxicity was tolerable. This regimen seemed to be one of the regimens which should be considered for the advanced or recurrent cervical cancer.     

Symptomatology, localization and treatment of recurrent cervical carcinoma

In a group of 367 women treated for invasive carcinoma of the cervix tumor recurrence was discovered at an asymptomatic stage in 16 (23%) patients. The tumor recurrence was localized to the pelvis in 29 (41%) cases, in the vaginal wall in 3 (4%) cases, and 39 (55%) patients had distant metastases (with or without recurrent tumor in the pelvis). Curative treatment (surgery, n = 2; radiotherapy, n = 8) was applied in 5/29 (17%) patients whose recurrent disease was confined to the pelvis, in all 3 patients with vaginal recurrence and in 2/39 (5%) of the patients with distant metastases. Permanent remission (follow-up > 36 months) was observed in 2 patients with vaginal recurrence and in one with central recurrence. Temporary complete remission (mean 22 months, range 12–30 months) was observed in 3 patients (2 with central recurrence and one with vaginal recurrence). In 20 (69%) of the patients with central or locoregional recurrence, the primary treatment had been so radical (including adjuvant postoperative or full radiotherapy) that surgical treatment or radiotherapy of the recurrence was not considered possible or worthwhile; moreover, 4 of the patients were older than 80 years of age. In retrospect, exenterative treatment could have been considered in 14 patients (< 70 years) and based on 50% operability, could have led to a cure in 2 to 4 patients with tumor recurrence in the pelvis without distant metastases. Chemotherapy was applied to 10 patients, one of whom went into complete remission of lung metastases (follow-up 108 months).     

A phase II study of ifosfamide and bleomycin in advanced or recurrent cervical carcinoma

Thirty-seven patients with advanced or recurrent cervical squamous cell carcinoma were treated with ifosfamide 1.5 g m⁻² on days 1–5 (with mesna as a uroprotector), and bleomycin 30 mg on day 1, every 3 weeks. A partial response rate of 21% (95%CI: 6–36%) was obtained in patients who had not received prior chemotherapy, with a median duration of response of 5 months. No complete responses were seen. The median survival of all patients was 6 months. Nausea and vomiting, white cell suppression and encephalopathy were the main toxic effects. The results suggest that the addition of bleomycin to ifosfamide is not advantageous and increases toxicity, and that the interaction between these two agents is not contributory to the activity of the bleomycin, ifosfamide and cisplatin combination regimen (BIP). The potentially more severe toxicity of combination regimens must be considered when treating this group of patients.     

Management of recurrent cervical cancer

Treatment for cervical cancer is very successful, especially in early stages. However, most patients presenting in late stages of disease will experience recurrence. The prognosis of recurrent disease is very poor and treatment options are limited. The diagnosis of recurrence may be apparent or difficult, but determining the extent of disease is always complex. Routine follow-up of asymptomatic patients has other objectives and is not a reliable way to detect recurrences. Symptomatic patients require extensive investigation to detect the extent of the disease. For patients with central pelvic recurrences, exenteration offers the prospect of survival in more than one-third of cases. Newer developments include laterally extended endopelvic resection that may become an option for patients with more extensive pelvic recurrence. For patients with recurrences of cervical cancer, the roles of second-time radiotherapy or postradiation chemotherapy are very limited. Palliative treatment is important for all patients with untreatable disease. Pain relief forms a central part of palliative care. Caregivers also experience emotional feelings and probably function best in a system offering strong colleageal support.     

复发性宫颈癌的治疗

宫颈癌是世界范围内最常见的女性生殖系统恶性肿瘤,严重威胁女性的生命。在发展中国家占女性癌症死亡率的第二位。宫颈癌治疗失败的主要原因是局部复发和远处转移。复发性宫颈癌患者预后差、5年生存率低。因此,复发性宫颈癌的治疗成为临床关注的重点。     

Results of cisplatin, adriamycin and etoposide chemotherapy in patients with recurrent and metastatic endometrial cancer

The efficacy of the combination treatment of cisplatin, adriamycin and etoposide were retrospectively evaluated in 26 recurrent or metastatic endometrial cancer patients. One hundred and twenty-three treatment courses were observed. Patients received 20 mg/m2 cisplatin and 80 mg/m2 etoposide by continuous i.v. infusion for three days and adriamycin 40 mg/m2 i.v. the second day. Treatment courses were repeated every four weeks. Megestrol acetate, 160 mg/day, was added in six patients who had positive progesterone receptors. Ten (38.5%) women had complete and three (11.5%) patients had partial response with an overall response rate of 50%. Median follow-up was 24 months. Surviving patients were alive for four months and six years. Toxicity was mainly hematological and gastrointestinal ulcerations and stomatitis were also observed.