During the last century, the mainstay for the treatment of uterine cervix cancer has been via two main primary treatment modalities, these being radical surgery (radical hysterectomy and regional lymph nodes dissection) and radiotherapy. Generally, radical surgery is restricted to stages I and IIa of FIGO (the International Federation of Gynecology and Obstetrics) Classification, while radiotherapy may be applied to all stages of cervical cancer. In 1999 the National Cancer Institute Clinical Announcement established concurrent chemoradiotherapy as a new primary treatment modality, which is the focus of this review.
Cervix Neoplasms/*therapy ; Combined Modality Therapy ; Female ; Human

Despite effective screening methods for detecting pre- malignant diseases of the cervix, cervical cancer remains a leading cause of cancer mortality in women globally. There has been a dramatic decline in the age adjusted death rate from cervical cancer in the United States, where cervical cancer has declined from the leading cause of cancer mortality in women prior to 1940 to a point where it is a relatively uncommon cause of cancer mortality today. Despite these advances in screening and early detection reported in the United States, intraepithelial disease detection rates in many non-industrialized countries remain low because screening programs are generally lacking. As a result most cancers detected in many underdeveloped areas of the world are advanced at diagnosis. Furthermore, in such countries there may be inadequacies in physicians trained in the most effective means of treating cervical cancer, technical support required for the effective delivery of radiation therapy or the administration of chemotherapy, and modern equipment required for optimal treatment with radiation therapy. Thus cure rates for women with cervical cancers in many areas of the world remain low.
Cervix Neoplasms/*therapy ; Clinical Trials ; Combined Modality Therapy ; Female ; Human

Neoadjuvant and adjuvant chemotherapies are used adjunctively with surgery or radiation and are among the treatment options that are now employed for reducing treatment failure in early-stage cervical cancers with high-risk prognostic factors. Adjuvant therapies have been reported to significantly improve survival than would otherwise be possible with surgery or radiotherapy alone. However, for advanced cervical cancers, sequential or concurrent chemo-radiotherapy does not appear to significantly increase survival. The combination of radiotherapy with IFN-a2a and RA in the treatment of patients with locally advanced cervical cancer showed high response rates, however this should be confirmed in larger studies. Recent reports show that postoperative adjuvant radiotherapy has no benefit in survival, but that postoperative adjuvant chemotherapy has improved survival. Toxicities and the optimum number of cycles of neoadjuvant and adjuvant chemotherapy, as well as biologic therapy, will follow along with individualized treatment based on high-risk prognostic factors. Although more comprehensive studies and longer follow up will be required for complete evaluation of these adjuvant therapies, preliminary results are promising.
Biological Products/therapeutic use ; Cervix Neoplasms/drug therapy* ; Chemotherapy, Adjuvant* ; Female ; Human ; Risk Factors

Skin metastasis from carcinoma of uterine cervix is extremely rare and its incidence is reported as 0.1~1.3%. Common pattern of occurrence is multiple nodules in abdomen, external genitalia, or lower extremeties. It is believed that the pathogenesis of skin metastasis is a result of retrograde spread of the tumor secondary to lymphatic obstruction. Treatment of skin metastasis may consist of surgical excision, local irradiation, or chemotherapy, but the prognosis is very poor and median survival is about 3 months. We have experienced such a case and report the case with brief review of literatures.
Abdomen ; Cervix Uteri ; Drug Therapy ; Female ; Genitalia ; Incidence ; Neoplasm Metastasis* ; Prognosis ; Skin* ; Uterine Cervical Neoplasms*

The majority of patients with recurrent cervical cancer are incurable and treatment is based on the type of primary therapy delivered. Only a very small percentage of the patients with recurrent cervical cancer following primary radiotherapy will have central pelvic recurrences that are amenable to surgical resection and curable by pelvic exenteration. These procedures should be undertaken only after the completion of exhaustive attempts to exclude extrapelvic disease.
Cervix Neoplasms/drug therapy/mortality/*surgery ; Female ; Human ; Neoplasm Recurrence, Local/drug therapy/mortality/*surgery ; Pelvic Exenteration/adverse effects/methods

PURPOSE: This study was conducted to investigate the level of nausea & vomiting, anorexia and food intake during the periods of chemotherapy and 14 days after discharge. METHOD: The subjects were 40 cancer patients(cervix cancer : 20 patients, stomach cancer: 20 patients) who had chemotherapy with Cisplatin & 5-Fu. Data were analyzed by mean & standard deviation, ANCOVA. RESULT: 1. The severity of nausea & vomiting with anorexia in cancer patients receiving chemotherapy was the highest at the 3rd day and then it gradually decreased. At the 14th day after discharge, nausea & vomiting with anorexia still remained with very low levels. 2. The amount of food intake was the lowest on the 3rd day and then gradually increased. However, it was 53.3-72.5% of the ordinary food intake on the 14th day after discharge. Calorie intake was 625.31 Kcal on the 3rd day and 1130.92 Kcal on the 7th day after discharge. 3. There were no significant differences in nausea & vomiting, anorexia, food intake, calory intake between those with cervix cancer and stomach cancer. CONCLUSION: In cancer patients nausea & vomiting and anorexia were severe and food intake was very poor during chemotherapy but afterwards they were gradually improved, but were not completely recovered on the 14th day after discharge. Therefore the nursing intervention regarding the increase of food intake was necessary during chemotherapy and after discharge.
Anorexia* ; Cervix Uteri* ; Cisplatin ; Drug Therapy* ; Eating* ; Female ; Fluorouracil ; Humans ; Nausea* ; Nursing ; Stomach Neoplasms* ; Stomach* ; Uterine Cervical Neoplasms* ; Vomiting*

Neoadjuvant chemotherapy prior to definitive radical surgery or radiotherapy may be effective in reducing tumor volume or clinical stage and may even enhance pelvic control and survival. However, there are significant limitations to the use of neoadjuvant therapy in the non-responder group. They include delayed total treatment course, the presence of drug resistant clones which result in accelerated tumor growth, and limited bone marrow reserve for subsequent definitive therapy. Thus, there is a need to identify parameters providing a more precise indication of the response to neoadjuvant chemotherapy in patients with invasive cervical cancer. From Jan. 1995 to Jan. 1996, neoadjuvant chemotherapy with 3 courses of cisplatin and vincristine was used in 32 patients with invasive cervical cancer (FIGO stage Ib to IIIb; tumor size greater than 2 cm). Prior to chemotherapy, quantitative tissue levels of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene protein were measured by using an enzyme-linked immunosorbent assay (ELISA). Tumor size was estimated before and after chemotherapy. Relations between oncoproteins and reductions of tumor size were evaluated. Tumor size prior to neoadjuvant chemotherapy did not show any correlation with either the concentrations of EGFR or c-erbB-2 oncoprotein. As well, the tumor reduction index did not manifest any correlation with EGFR, it did had an inverse linear correlation with the c-erbB-2 oncoprotein levels (Rs = -0.71, P < 0.05). The results of this study suggest that c-erbB-2 oncoprotein is associated with a reduced response to neoadjuvant chemotherapy in primary treatment of invasive cervical cancer and may be useful in directing therapeutic approaches.
Adult ; Aged ; Carcinoma/metabolism* ; Carcinoma/drug therapy* ; Cervix Neoplasms/metabolism* ; Cervix Neoplasms/drug therapy* ; Female ; Human ; Middle Age ; Neoadjuvant Therapy* ; Receptor, Epidermal Growth Factor/metabolism* ; Receptor, erbB-2/metabolism* ; Treatment Outcome

OBJECTIVE: Telomerase is a ribonucleoprotein that synthesizes TTAGGG repeats onto chromosome ends. The expression of telomerase is thought to be required for cellular immortality and carcinogenesis. This study was conducted to examine the telomerase activation occurs in cervical carcinogenesis. METHODS: The standard telomeric repeat amplification protocol(TRAP) was used to examine telomerase activity in tissues of 10 normal cervix, 10 carcinoma in situ, and 21 invasive cervical carcinoma. RESULTS: Telomerase activity was detected in tissues of 16/21(76.2%) invasive carcinoma, in 5/10(50.0%) carcinoma in situ, and in 3/10(30.0%) normal cervix. But the degree of telomerase activity in normal cervix was weak. There was significant difference in 3 groups(p<0.05). The results of neoadjuvant chemotherapy in 10 invasive cervical carcinoma were as follows. In 8 cases of which tumor size decreased more than 50%, 5 were positive for telomerase. In 2 cases that didn't respond to chemotherapy by tumor size, 1 was positive for telomerase. There was no significant difference between 2 groups. All of the 5 cases that had pelvic lymph node metastasis revealed positive telomerase activity, and the 11 cases of 16 cases that didn't have pelvic lymph node metastasis were positive for telomerase, but there was no significant difference in 2 groups. The positivity of telomerase activity in clinical stage of invasive cervical carcinoma was 73.3% in stage I(11/15), 75.0% in stage II(3/4), 100% in stage III(1/1), and 100% in stage IV(1/1), but there was no significant difference in each stages. CONCLUSION: Telomerase seems to be uniquely associated with malignant transformation of cervix and can be used as a tumor marker. Additional studies are needed to better clarify the biological significance of telomerase expression in cervical tumorigenesis.
Carcinogenesis ; Carcinoma in Situ ; Cervix Uteri ; Drug Therapy ; Female ; Lymph Nodes ; Neoplasm Metastasis ; Ribonucleoproteins ; Telomerase* ; Uterine Cervical Neoplasms*

OBJECTIVE: Paclitaxel, ifosfamide, and cisplatin have moderate single-agent activity in patients with metastatic or recurrent cancer of the uterine cervix. We administered a combination of these three agents (TIP) to patients with recurrent cervical carcinoma to evaluate its activity. METHODS: Forty-three patients were treated with ifosfamide (I) 1500 mg/m2 intravenously over 3 hours on Days 1-3, paclitaxel (T) 135 mg/m2 as a 3-hour intravenous infusion and cisplatin (P) 50 mg/m2 intravenously over 30 min on Day 1. The chemotherapy was repeated every 3 weeks. RESULTS: Thirty-five patients received at least three courses of treatment and were evaluable for response. Eighteen patients (51.4%) achieved an objective response, including 5.7% complete and 45.7% partial responses. The median time to progression and overall survival for all patients were 8.0 and 16.0 months, respectively. The site of recurrence relative to prior radiation field and histopathology (squamous vs other pathology) did not affect the response rate and survival. Patients treated with another chemotherapy regimen before the initiation of TIP regimen showed lower response rate (28.6% vs 66.6%, p=0.027) and shorter survival (14 month vs 25 month, p=0.028). Grade 3 or 4 toxicity included granulocytopenia in 13% of patients, anemia in 8%, thrombocytopenia in 5%. CONCLUSION: The TIP regimen is relatively well tolerated and moderately active in patients with recurrent carcinoma of the uterine cervix. Patients more likely to benefit are those who received TIP regimen for the first time after recurrence.
Agranulocytosis ; Anemia ; Cervix Uteri* ; Cisplatin* ; Drug Therapy ; Female ; Humans ; Ifosfamide* ; Infusions, Intravenous ; Paclitaxel* ; Recurrence ; Thrombocytopenia ; Uterine Cervical Neoplasms

OBJECTIVE: To determine the effects of neoadjuvant chemotherapy (5-fluorouracil plus cisplatin) on tumor cell morphology and apoptosis by analyzing the consecutive changes of apoptotic index (AI) and histology observed in the serially obtained cervical cancer tissues during the chemotherapy. METHODS: Cervical cancer tissues were obtained by punch biopsy just before starting the each cycle of neoadjuvant chemotherapy from five patients with locally advanced disease (stage IIb-IIIb), but previously untreated squamous cell carcinoma of uterine cervix. All patients were treated with three cycles of 5-fluorouracil (1,000 mg/m2 at day #1-5) and cisplatin (60 mg/m2 at day #1) at 3 weeks interval. All H & E stained cervical cancer tissue slides were scored for apoptotic index and observed for microscopic changes of tumor cells by a pathologist. RESULTS: After the first cycle of chemotherapy, AI was significantly increased (from 2 times to 8 times). And widespread injury to cytoplasm was observed and followed by karyorrhexis and karyolysis of nucleus of tumor cells. The size of tumor nests was reduced and it was also noted that fibrosis and infiltration of inflammatory cells were increased. The parts of tumor nests were replaced by mature squamous cells and the changes in nuclear morphologic features pointing in a more differentiated direction. But after the second cycle of chemotherapy, only one patient showed an increase in AI by 1.2 times over that after the first cycle of chemotherapy. The rest showed slight decreases in AI compared to that after the first cycle of chemotherapy. In addition, fewer microscopic morphologic changes of tumor cells induced by chemotherapy were observed after the second cycle of chemotherapy compared to those after the first cycle of chemotherapy. CONCLUSION: We found that AI hardly increased or rather decreased, and that microscopic changes of tumor cells were fewer after the second cycle of neoadjuvant chemotherapy compared to the situation after the first cycle of chemotherapy. Thus, we could deduce that chemoresistance might rapidly develop in cervical cancer cells after the first cycle of neoadjuvant chemotherapy using 5-fluorouracil and cisplatin. So we need to consider this problem when we treat the locally advanced cervical cancer patients with neoadjuvant chemotherapy using 5-fluorouracil and cisplatin.
Apoptosis ; Biopsy* ; Carcinoma, Squamous Cell ; Cervix Uteri ; Cisplatin* ; Cytoplasm ; Drug Therapy* ; Female ; Fibrosis ; Fluorouracil* ; Humans ; Uterine Cervical Neoplasms*