mesna and Uterine-Cervical-Neoplasms

Peripheral primitive neuroectodermal tumor (PNET) of the cervix uteri is extremely rare. Between 1987 and 2002, there have been eight cases described in the English literature. The treatment policies in these eight cases differed considerably, partly due to the rarity of the disease and to differing time periods of diagnosis and treatment.. At the end of 2002, a 21-year-old woman presented with a PNET of the cervix uteri at our institute, the Erasmus Medical Center. For the appropriate treatment in this case, we reviewed the literature and decided that the treatment should be different from the local surgical treatment followed by additional treatments as most of the earlier reports describe.. In view of the current knowledge of PNET belonging to the family of Ewing's sarcoma, and the improvement of treatment outcome in these tumors due to dose-intensive neo-adjuvant chemotherapy, patients with PNET of the cervix should be treated in accordance to the protocol for bony Ewing's sarcoma with multimodality therapy by means of induction chemotherapy, surgery, and consolidation chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Dactinomycin; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Mesna; Neoadjuvant Therapy; Neuroectodermal Tumors, Primitive, Peripheral; Uterine Cervical Neoplasms; Vincristine

To investigate the role of neoadjuvant chemotherapy followed by radiotherapy in locally advanced cervical cancer.. This study cites all known literature on the subject in the English language. Articles were selected for analysis by MEDLINE and CANCERLINE computer searches. In Phase II trials, the response rates of some selective series were analyzed. However, This article will specially emphasize the result of all Phase III randomized trials.. Several investigators did obtain promising results from Phase II trials of neoadjuvant chemotherapy, mostly cisplatin-based combinations, followed by radiotherapy. However, most Phase III trials failed to demonstrate any benefit in terms of loco-regional relapse and/or survival by up-front chemotherapy.. The role of neoadjuvant chemotherapy remains to be defined, and the search for more active new agents must be continued. The neoadjuvant setting is still experimental and could not be recommended as a standard treatment at the present.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cyclophosphamide; Female; Humans; Ifosfamide; Mesna; Mitomycins; Neoplasm Staging; Randomized Controlled Trials as Topic; Uterine Cervical Neoplasms; Vincristine

The stage-by-stage prognosis for cervical cancer patients has not improved in the past decades. Our research work concerning adjuvant chemotherapy for the early stages induced a pilot study with untreated patients in advanced stages. Patients were treated with carboplatin 300 mg/m2 plus ifosfamide 5 g/m2 on day 1. In cases of remission or no change, the therapy was repeated after 4 weeks. A third course was given only after further remission. After chemotherapy, patients were treated with surgery or radiotherapy according to feasibility. A total of 34 patients were admitted to this study. Thirty-two patients with 88 chemotherapy courses were evaluable for response and toxicity. Nineteen patients achieved remission; three achieved complete remission. The most common toxic effects were myelosuppression with grade four leukopenia (28%) and thrombocytopenia (13%). Alopecia (60%) was the main nonhematologic toxicity. In conclusion, we suggest that this regimen is as effective as other platin-containing regimens for squamous cell carcinoma of the cervix uteri, but its hematologic toxicity precludes its recommendation in an adjuvant setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Female; Humans; Ifosfamide; Leukopenia; Mesna; Middle Aged; Remission Induction; Thrombocytopenia; Uterine Cervical Neoplasms

The aim of this study was to determine the response rate, toxicity, operability, and surgical complication rate of neoadjuvant concomitant radiochemotherapy (cRCH) (ifosfamide + carboplatin) followed by radical hysterectomy plus external-beam radiotherapy with curative intention in locally advanced primary inoperable stages IIB and IIIB squamous cell cervical cancer.. Patients with cervical cancer from 8 departments were enrolled. Patients received 3 cycles of ifosfamide 1.2 mg/m (+mesna 20%) plus carboplatin (area under the curve = 4), every 21 days, and concomitant external-beam radiotherapy (50.4 Gy [1.8 Gy/d]). Operability and remission were evaluated by clinical gynecological examination in general anesthesia (magnetic resonance imaging was optional), 4 weeks after the third cycle of cRCH. In case of achieved operability, a radical hysterectomy with pelvic lymphadenectomy was performed within 6 weeks after cRCH. If surgery was not performed because of incomplete remission or patient preferences, vaginal brachytherapy (15 Gy [5 Gy/d]) was given additionally.. Forty-four patients were enrolled. Distribution of FIGO (International Federation of Gynecology and Obstetrics) tumor stage was as follows: IIB (19 patients) and IIIB (25 patients). All patients completed cRCH. Grade 3/4 hematologic toxicities (% of all cycles) were moderate: leukopenia, 7.3; thrombocytopenia, 2.4; and anemia, 3.2. In 13.8%, treatment cycles were delayed because of hematologic toxicity. Blood transfusions were given in 17.7% and granulocyte colony-stimulating factor in 39.5%. Overall, grade 3/4 nonhematologic toxicities were seldom (6.5%). Clinical overall response rate was 95.2%. Operability was achieved in 85.7%. Surgery was performed in 83.3%. Pathological response rates were as follows: pathological complete remission, 33.3%; partial remission, 63.3%; stable disease, 3.3%.. Our study demonstrates that cRCH is an effective and tolerable regimen in locally advanced cervical cancer treatment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Female; Humans; Hysterectomy; Ifosfamide; Mesna; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prospective Studies; Survival Rate; Treatment Outcome; Uterine Cervical Neoplasms

We undertook a randomized phase II trial to test whether the addition of paclitaxel (Taxol) to the cisplatin and ifosfamide (IP) combination could improve objective response (OR) rate, progression-free survival (PFS) and overall survival (OS) in patients with recurrent or metastatic cancer of the uterine cervix.. One hundred and fifty-three patients were randomly allocated to receive either the IP regimen (ifosfamide 1.5 g/m(2), daily, on days 1-3 and cisplatin 70 mg/m(2) on day 2) or the same combination with the addition of paclitaxel 175 mg/m(2) on day 1 [ifosfamide, paclitaxel and cisplatinum (ITP) regimen]. Cycles were administered every 4 weeks on an outpatient basis.. A modest increase in neurotoxicity was observed with the triplet combination. OR rate was significantly higher in the ITP group (59% versus 33%, P = 0.002). Median PFS was 7.9 and 6.3 months for patients in the ITP and IP arms, respectively (P = 0.023). Median OS was 15.4 months and 13.2 months in the ITP and IP arms, respectively (P = 0.048). In multivariate analysis, the triplet yielded a hazard ratio of 0.70 for relapse or progression (P = 0.046) and 0.75 for death (P = 0.124) compared with the doublet.. The ITP combination merits further investigation in randomized phase III studies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Female; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Metastasis; Paclitaxel; Uterine Cervical Neoplasms

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Ifosfamide; Mesna; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Survival Analysis; Uterine Cervical Neoplasms; Vinblastine

A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Adjuvant; Cisplatin; Female; Follow-Up Studies; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Staging; Prospective Studies; Radiotherapy, Adjuvant; Remission Induction; Survival Rate; Uterine Cervical Neoplasms

Thirty patients with advanced squamous cell carcinoma of the cervix were included in a phase II study with cisplatin (DDP) and ifosfamide (IF)/mesna. They received a median of 4 courses of chemotherapy and were all evaluable for response and toxicity. Each cycle consisted of 2,500 mg/m2 IF i.v. days 1-5; mesna 500 mg/m2 i.v. at hours 0 and 2, and 1,000 mg/m2 per os at hours 6 and 10, days 1-5; DDP 20 mg/m2 i.v., days 1-5. Cycles were repeated every 4 weeks. One patient obtained CR and 14 PR giving an overall response rate of 50%. Mean duration of response was 21 months. Anemia grade 3 developed in 7 patients, leukopenia grade 3 in 9 patients and grade 4 in one patient; thrombopenia grade 3 in 2; creatinine clearance grade 3 in one; CNS grade 3 in one and cystitis grade 3 in one patient. Overall median survival time was about 25+ months (3-63+); after a follow-up of 70 months, 11 patients (37%) are still alive with a median survival of 31+ months. IF plus DDP seems to be a good combination for treatment of advanced cervical cancer, with acceptable tolerance and response rate.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Ifosfamide; Mesna; Middle Aged; Survival Rate; Uterine Cervical Neoplasms

Our objective was to determine the activity of ifosfamide and mesna in women with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy.. This is a phase II drug study in which the starting dose of ifosfamide was 1.5 gm/m2 daily intravenously for 5 days. The starting dose of ifosfamide was reduced to 1.2 gm/m2 daily in patients who had received prior radiotherapy. The uroprotector mesna was given intravenously with, and at 4 and 8 hours after, the administration of ifosfamide. Each dose of mesna was 20% of the total daily dose of ifosfamide.. Fifty-six patients were placed in the study; 52 were evaluable for toxicity and 51 for response. Twenty-eight (54.9%) patients had previously undergone surgery and 46 (90.2%) had received radiotherapy before this trial. Gynecologic Oncology Group grade 3 or 4 granulocytopenia occurred in 7 (13.5%) patients, and 2 (3.9%) had grade 3 thrombocytopenia. Six (11.5%) patients had grade 3 or 4 neurotoxicity. Complete response was observed in 2 (3.9%) patients and partial responses in 6 (11.5%) patients, for a total response rate of 15.7% (95% confidence interval 7.02% to 28.59%).. This response rate is higher than that reported by the Gynecologic Oncology Group in patients with previously treated squamous carcinoma of the cervix. Our findings fail to confirm that ifosfamide is a highly active agent in patients with squamous carcinoma of the cervix as reported by others; nonetheless, the observed activity of this drug deserves further study in combination therapy of squamous carcinoma of the cervix.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Ifosfamide; Mesna; Middle Aged; Uterine Cervical Neoplasms

A phase II trial of ifosfamide (IFX) and mesna was conducted by the GOG in patients with recurrent or advanced nonsquamous carcinoma of the cervix. A starting dose of 1.5 g/m2 IFX iv daily for 5 days and 300 mg/m2 mesna iv every 4 hr with three doses daily after IFX were given. In patients who had received prior radiotherapy or chemotherapy, the starting dose of IFX was reduced to 1.2 g/m2. Forty-six patients were entered, and 41 are evaluable for toxicity. Forty patients are evaluable for response. Age range was 30-72 yr. GOG performance status was 0-1 for all but 2 patients. Fifteen patients (37.5%) developed GOG grade 3 or 4 granulocytopenia, and 1 developed grade 4 thrombocytopenia. One patient developed transient renal insufficiency. There was one complete response and five partial responses (12.5%) for a response rate of 15.0%. Median response duration was 4.2 months (range, 1.7-22.6 months). Three responses were seen in areas with pelvic disease only. Three responses were observed in extrapelvic sites. IFX possesses activity which compares favorably with that of other agents in this disease.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma; Female; Humans; Ifosfamide; Mesna; Middle Aged; Uterine Cervical Neoplasms

The stage-by-stage prognosis for cervical cancer patients has not improved in the past decades. Our research work concerning adjuvant chemotherapy for the early stages induced a pilot study with untreated patients in advanced stages. Patients were treated with carboplatin 300 mg/m2 plus ifosfamide 5 g/m2 on day 1. In cases of remission or no change, the therapy was repeated after 4 weeks. A third course was given only after further remission. After chemotherapy, patients were treated with surgery or radiotherapy according to feasibility. A total of 34 patients were admitted to this study. Thirty-two patients with 88 chemotherapy courses were evaluable for response and toxicity. Nineteen patients achieved remission; three achieved complete remission. The most common toxic effects were myelosuppression with grade four leukopenia (28%) and thrombocytopenia (13%). Alopecia (60%) was the main nonhematologic toxicity. In conclusion, we suggest that this regimen is as effective as other platin-containing regimens for squamous cell carcinoma of the cervix uteri, but its hematologic toxicity precludes its recommendation in an adjuvant setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Female; Humans; Ifosfamide; Leukopenia; Mesna; Middle Aged; Remission Induction; Thrombocytopenia; Uterine Cervical Neoplasms

In July 1985, the Gynecologic Oncology Group initiated a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received ifosfamide 1.5 g/m2/d intravenously (IV) for 5 days. Mesna was given IV every 4 hours for three doses after ifosfamide administration at a dose of 20% of the daily ifosfamide dose. All patients with ovarian cancer and 87% of those with cervical cancer had had prior platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2/d in those who had had prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses (CRs). Response duration was 2.1 to 20.3+ months (median, 6.9+ months). In squamous carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients had partial responses (PRs) of 1.8-, 2.2-, and 3.1-month duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) had CRs and 3 (11.5%) had PRs, for an overall response rate of 30.7%. Response duration was 1.4+ to 8.6 months, with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Evaluation; Female; Genital Neoplasms, Female; Hematologic Diseases; Humans; Ifosfamide; Leiomyosarcoma; Mesna; Middle Aged; Multicenter Studies as Topic; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Remission Induction; Uterine Cervical Neoplasms; Uterine Neoplasms

Several studies in solid tumors have shown that expression of excision repair cross-complementation group 1 (ERCC1) and class III β-tubulin (TUBB3) can predict response to chemoradiotherapy and might be prognostic factors. We assessed the role of ERCC1 and TUBB3 expressions as predictive and prognostic factors in locally advanced cervical squamous cell carcinoma (LACSCC) patients treated with different neoadjuvant regimens.. ERCC1 and TUBB3 were detected in 88 patients with LACSCC by immunohistochemical analysis. Sixty-two patients were included in 3 different prospective trials and grouped as follows: vinorelbine or docetaxel (group A, n = 44) and ifosfamide-vinorelbine-cisplatin (group B, n = 18). Both groups were compared with standard cisplatin chemoradiotherapy (group C, n = 26). Clinical data at baseline, disease-free survival (DFS) and overall survival (OS) were also collected. Univariate and multivariate Cox models were used to analyze the risk factors.. Thirty-five patients (39.8%) and 18 (20.5%) had high ERCC1 and TUBB3 expression, respectively. Both proteins were overexpressed in tumors with unfavorable characteristics. High ERCC1 was associated with advanced FIGO stage (p = 0.034) and progressive disease (49% vs. 28%). Poor DFS (p = 0.021) and OS (p = 0.005) were observed in group C patients with high ERCC1 expression. Multivariate analysis showed that ERCC1 expression, FIGO stage and pretreatment hemoglobin level were significant prognostic factors (p = 0.002, p = 0.008 and p = 0.005, respectively).. ERCC1 expression could be a predictive and prognostic factor in LACSCC patients who receive cisplatin monotherapy. Conversely, TUBB3 had no impact on survival in patients treated with antimicrotubule agents.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Clinical Trials, Phase II as Topic; Disease Progression; Disease-Free Survival; DNA-Binding Proteins; Endonucleases; Female; Gene Expression Regulation, Neoplastic; Humans; Hysterectomy; Ifosfamide; Kaplan-Meier Estimate; Mesna; Middle Aged; Neoplasm Proteins; Palliative Care; Prognosis; Radiotherapy, Adjuvant; Tubulin; Uterine Cervical Neoplasms; Vinblastine; Vinorelbine

Twenty-five patients, ranging from 21 to 61 years of age (median = 45 years), with histologically proven recurrent and advanced cervical cancer were treated with chemotherapy using a combination of bleomycin, ifosfamide, and cis-platinum (BIP). Twenty-one patients were evaluable for response. Ninety percent of patients achieved a subjective response. An objective response was noted in 14 of 21 (66.6%) patients: complete in 4 (19%) and partial in 10 (47.6%). Side effects were mainly nausea/vomiting, alopecia, myelosuppression, reversible encephalopathy, and impaired renal function. One patient died from the toxic effects of chemotherapy. These results indicate that BIP is an active combination in recurrent cervical cancer with acceptable toxicity.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Squamous Cell; Cisplatin; Dose-Response Relationship, Drug; Female; Humans; Ifosfamide; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mesna; Middle Aged; Neoplasm Recurrence, Local; Uterine Cervical Neoplasms

Twenty-four evaluable patients with recurrent or advanced squamous carcinoma of the cervix were treated with ifosfamide (IFX) and mesna every 3 weeks. The initial dose of IFX was 1.5 g/m2 q.d. Days 1-5. Mesna was given by continuous infusion (1.5 g/m2/day Days 1-6). Seventy-four courses of treatment were given to 24 patients. All patients were evaluable for toxicity and response. The median survival was 26 weeks from initiation of chemotherapy. There were 4 complete responders (CR); there was 1 partial responder. The response rate was 20.8% (CI, 4-38%). One CR patient remains in clinical remission 30 months after initiation of therapy. The other 3 responders recurred after a disease-free interval of 8, 12, and 18 weeks. WBC below 3000/mm3 occurred in 19 patients and was life threatening (below 1000/mm3) in 5 patients. One patient had life-threatening hemorrhagic cystitis. Eleven patients developed CNS symptoms during treatment including somnolence, coma, and acute delirium.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Drug Evaluation; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Recurrence, Local; Nervous System Diseases; Uterine Cervical Neoplasms

A Phase II study of VP-16 (etoposide), ifosfamide/mesna, and cisplatin (VIP) in advanced and recurrent carcinoma of the cervix was initiated March 1989. VP-16, 75 mg/m2, ifosfamide, 1.0 g/m2, and cisplatin, 25 mg/m2, were administered intravenously daily for 3 consecutive days, every 28 days to a maximum of six cycles. Fourteen patients were entered on protocol. Eight patients had objective responses, all complete. Response duration ranged from 7+ to 24+ months. The chemotherapy was well-tolerated. Hematologic toxicity was the major toxicity and was manageable. VIP appears to be active in advanced carcinoma of the cervix.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Etoposide; Female; Hematologic Diseases; Humans; Ifosfamide; Mesna; Middle Aged; Neoplasm Recurrence, Local; Uterine Cervical Neoplasms

This study was carried out to assess the efficacy of high-dose ifosfamide/mesna (HDIFM) in the treatment of advanced or recurrent cancer of the cervix. In all, 18/21 evaluable patients with advanced or inoperable cervical cancer were included. The mean age was 42 years (range, 31-58 years); and the International Federation of Gynecology and Obstetrics (FIGO) stage was III in 10 patients and IV in 11. The Karnofsky performance status ranged between 70 and 90, with a median of 77. Ten patients had previously been treated with surgery, radium and cobalt (8) or cobalt alone (2). Therapy consisted of 3.5 g/m2, ifosfamide (IFO) given in an 8-h i.v. infusion on days 1-5 and mesna at 20% of the IFO dose, given i.v. at 0, 2, 4, 6 and 8 h, followed by mesna at 40% of the IFO dose by the oral route at 10 and 12 h on days 1-5. For evaluation purposes, patients received at least two cycles. Toxicity was registered in 137 cycles and was mild to moderate. Three complete (16.6%) and six partial (33.3%) responses were observed (50%), but 66% of them occurred in areas that had not previously been irradiated. The median duration of response was 14 months and the overall median survival was 15+ months (18+ months for responders). The Karnofsky scale after treatment ranged from 90 to 100. The results of this study indicate that HDIFM is well tolerated, giving a high percentage of remission (50%) and significantly improving the quality of life.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Female; Humans; Ifosfamide; Mercaptoethanol; Mesna; Middle Aged; Uterine Cervical Neoplasms

Starting in July 1985, the Gynecologic Oncology Group conducted a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received 1.5 g/m2 i.v. ifosfamide daily for 5 days. Mesna was given i.v. q4h x 3 following ifosfamide; each dose was 20% of the daily ifosfamide dose. All patients with ovarian and 87% of those with cervical cancer had previously undergone platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2 daily in all patients who had received prior chemo- or radiotherapy. In epithelial ovarian carcinoma, responses were observed in 8 (20.0%) of 41 evaluable patients, with 3 (7.0%) complete responses. Response duration was 2.1-20.3+ months, with a median of 6.9+ months. In squamous-cell carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients showed partial responses of 1.8, 2.2, and 3.1 months' duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) achieved complete and 3 (11.5%) showed partial responses, for an overall response rate of 30.7%. Response duration was 1.4(+)-8.6 months, with a median of 3.8 months. Toxicity included two deaths due to renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Topics: Antineoplastic Agents; Carcinoma; Drug Evaluation; Female; Humans; Ifosfamide; Mercaptoethanol; Mesna; Middle Aged; Ovarian Neoplasms; Sarcoma; Uterine Cervical Neoplasms

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.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Evaluation; Drugs, Investigational; Female; Humans; Ifosfamide; Mesna; Middle Aged; Recurrence; Uterine Cervical Neoplasms

The Gynecologic Oncology Group initiated a series of phase II trials of ifosfamide/mesna in women with advanced or recurrent gynecologic malignancies in July 1985. Previously untreated patients received ifosfamide, 1.5 g/m2/d, intravenously (IV) for five days. Mesna was given IV in three doses every four hours after ifosfamide; each dose was 20% of the daily ifosfamide dose (ie, 300 mg/m2). All patients with ovarian and 87% of those with cervical cancer had undergone platinum-based therapy previously. Because of the toxicity encountered in previously treated ovarian cancer patients, the dose of ifosfamide was reduced to 1.2 g/m2/d in patients who had received prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (21.6%) of 37 evaluable patients with three (8.1%) complete responses. Response duration was 2.1 to 20.3+ months with a median of 6.9+ months. In squamous carcinoma of the cervix, three (11.1%) of 27 evaluable patients had partial responses of 1.8, 2.2, and 3.1 months' duration. Of 29 untreated patients with mixed mesodermal tumors of the uterus, five (17.9%) had complete and four (14.3%) had partial responses for an overall response rate of 32.2%. Response duration was 1.4+ to 8.6 months with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Drug Evaluation; Female; Humans; Ifosfamide; Mercaptoethanol; Mesna; Middle Aged; Neoplasms, Germ Cell and Embryonal; Organoplatinum Compounds; Ovarian Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms

Thirty patients with symptomatic, progressive squamous cell carcinoma of the uterine cervix no longer amenable to surgery or radiotherapy were entered in a phase II study of ifosfamide (IFX). Patients were treated with IFX (5 g/m2 iv given over 24 hours) and concomitant mesna (total dose, 9.2 g/m2 iv given over 36 hours) every 21 days. One complete response (duration, 10+ months) and nine partial responses were observed, with an overall median response duration of 6.5 months. The median survival of responding patients was 11 months. Objective response rates for lesions arising in previously irradiated sites (four of 22) were significantly lower than for lesions arising in nonirradiated sites (15 of 28) (P = 0.018). There were two treatment-related deaths: one due to leukopenia-associated infection in a patient with peritonitis and severe central nervous system toxicity and one due to central nervous system toxicity without complicating factors. One other patient developed severe but reversible encephalopathy. In all remaining patients hemorrhagic cystitis and hematological and gastrointestinal toxic effects were predictable and manageable. Treatment was delayed for 1 week due to toxicity on seven of 101 occasions: four of these delays were due to mild, reversible impairment of renal function and three were due to leukopenia. Complete though reversible alopecia occurred in 22 of 30 patients. The results indicate that IFX is active in cervical cancer and deserves further study in this setting.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Central Nervous System Diseases; Drug Evaluation; Female; Hematologic Diseases; Humans; Ifosfamide; Lung Neoplasms; Mesna; Middle Aged; Nausea; Neoplasm Recurrence, Local; Uterine Cervical Neoplasms

Ifosfamide and mesna were administered to 77 patients with advanced malignancies. Seven (9%) experienced a severe but reversible encephalopathy. In 56% of patients in whom EEG data was available, characteristic changes were seen with or without mild clinical toxicity. Discriminant analysis identified low serum albumin concentration, high serum creatinine concentration and the presence of pelvic disease as variables which predispose patients to the development of severe encephalopathy. A nomogram has been constructed which can be used to determine the probability that an individual patient may be given ifosfamide and mesna safely. This has important implications for the clinical use of a highly active chemotherapy regimen.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Diseases; Electroencephalography; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Soft Tissue Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms