mesna and Carcinoma--Squamous-Cell

Squamous cell carcinoma of the head and neck (SCCHN) is a functionally and cosmetically devastating tumor, and its treatment and the economic costs associated with aggressive treatment are substantial. Even with aggressive standard local surgery, radiotherapy, or both, locally advanced tumors recur in approximately two thirds of patients and the prognosis for those whose disease recurs or metastasizes is dismal. Newer chemotherapeutic agents such as ifosfamide and taxanes (paclitaxel [Taxol; Bristol-Myers Squibb Company, Princeton, NJ] and docetaxel) have shown higher response rates than those seen with conventional agents and renew hope of prolonged survival, improved quality of life, and greater convenience. We recently conducted two consecutive phase II studies using paclitaxel/ifosfamide/cisplatin and paclitaxel/ifosfamide/carboplatin for patients with recurrent or metastatic SCCHN. These two regimens yielded high response rates (including complete responses) and appear to be promising therapies for SCCHN. This report describes our experience with these two regimens, including a comparison of their toxic effects.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials as Topic; Head and Neck Neoplasms; Humans; Ifosfamide; Mesna; Neoplasm Recurrence, Local; Paclitaxel; Taxoids

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

We investigated dose-dense docetaxel and cisplatin in patients with measurable non-small cell lung cancer in a randomized phase II study without [A] or with [B] a putative chemoprotective agent, BNP7787.. Chemotherapy-naive patients with stage IIIB (effusion) or IV, performance status 0 to 1, and adequate organ function were eligible. Treatment with docetaxel 75 mg/m followed by cisplatin 75 mg/m over 1 hour day 1 with darbepoetin 200 mug day 1 and pegfilgrastim 6 mg day 2 without/with BNP7787 before cisplatin was repeated every other week for up to 6 cycles. The primary end point was to differentiate between grade >/=2 neurotoxicity rates of 30% on [A] and 10% on [B]. Feasibility was prospectively defined as febrile neutropenia in <10% of patients and /=2 occurred in 32% on [A] and 29% on [B]. The incidence of febrile neutropenia was 4% on [A] and 3% on [B]. Treatment delays occurred in 13% and 20% of patients on [A] and [B], respectively. Completion rates for 3/6 cycles were 84%/51% on [A] and 84%/53% on [B]. Objective response rates were 55% on [A] and 51% on [B]. Median progression-free/overall survival times were 5.5/10.7 on [A] and 6.5/14.1 month on [B].. This dose-dense treatment regimen is active, feasible, and tolerable. Its further investigation in the curative setting in non-small cell lung cancer should be considered. BNP7787 did not result in significant protection from neurotoxicity.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Darbepoetin alfa; Docetaxel; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erythropoietin; Feasibility Studies; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Mesna; Middle Aged; Neoplasm Staging; Neutropenia; Polyethylene Glycols; Prognosis; Recombinant Proteins; Survival Rate; Taxoids

This Phase II trial was conducted to determine the response rate, particularly of the primary sites, tolerability, and toxicity of induction chemotherapy of paclitaxel, ifosfamide, and carboplatin for patients with previously untreated locally advanced squamous cell carcinoma of the head and neck (SCCHN). We also hypothesized that improved complete response (CR) rates with the induction chemotherapy may render better survival rates with subsequently delivered definitive local treatment.. All eligible patients with locally advanced SCCHN received two courses of induction chemotherapy and underwent repeated head and neck examination and computed tomography or magnetic resonance imaging scans. If the patients achieved responses (CR or partial [PR]), they received two more courses of chemotherapy before undergoing definitive local treatment. Induction chemotherapy consisted of paclitaxel (T; 175 mg/m(2) in a 3-hour infusion) on Day 1, ifosfamide (I; 1000 mg/m(2) in a 2-hour infusion) on Days 1-3 with intravenous mesna (200 mg/m(2) before and 400 mg/m(2) after ifosfamide), and carboplatin (C) using the Calvert formula for the area under the plasma concentration-versus-time curve of 6 on Day 1, repeated every 3-4 weeks. Prophylactic hematopoietic growth factors or antibiotics were not used in this study. Definitive local treatment was given based on the investigators' preference.. Fifty-four patients were registered and 52 patients were assessable for response to induction chemotherapy; 2 were not evaluable. After four courses of induction chemotherapy, the CR rates of the primary and lymph node sites were 60%, and 41%, respectively. For both primary and lymph node sites, there were 31% CRs and 50% PRs with an overall response rate of 81%. Five (9%) patients developed neutropenic fever, all of whom recovered with antibiotic therapy. Two (4%) patients had infection without neutropenia and recovered without any complication. Grade 3/4 thrombocytopenia and anemia occurred in three (6%) and four (7%) patients, respectively. Grade 3/4 fatigue developed in four (7%), arthralgia/myalgia in two (4%), peripheral neuropathy in two (4%), and orthostatic hypotension in two (4%) patients. One patient died of severe anaphylaxis although a maximized resuscitation effort was made. With a median follow-up of 22 months, the organ preservation rate was about 81% (42 of 52 patients). Although survival rates were not primary end points in this study, with a median follow-up of 22 months, 43 (83%) patients are still alive. Overall 1 and 2-year survival rates were 88% and 82%, respectively. Disease-free 1 and 2-year survival rates were 88% and 77% respectively.. TIC induction chemotherapy is associated with a high CR rate at the primary sites and with excellent survival and organ preservations rates with subsequently delivered definitive local therapy. The regimen was also well tolerated in the majority of patients. The TIC regimen should be developed further in the context of induction chemotherapy followed by concomitant chemoradiotherapy or with specific molecular targeted agents.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Ifosfamide; Male; Mesna; Middle Aged; Paclitaxel; Survival Rate; Taxoids

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

To evaluate the efficacy and toxicity of a brief, intensive cisplatin-based outpatient chemotherapy regimen with filgrastim and megestrol acetate support for patients with stage IIIB and IV non-small cell lung cancer (NSCLC) and a favorable performance status. Thirty patients with no prior chemotherapy were enrolled in this phase II protocol. Patients received cisplatin 50 mg/m2, ifosfamide 2 g/m2, mesna, and a 7-day course of oral etoposide beginning on days 1, 15, 29, 43. and 57 for a total treatment duration of 10 weeks. Filgrastim was administered for 7 days after each course of oral etoposide. Megestrol acetate 250 mg PO was administered throughout the duration of chemotherapy. Thirty patients were evaluable for toxicity and 27 for response. Among those evaluable for response, partial remission occurred in 11 (41%) patients, and median survival was 10.5 months. Nadir neutrophil count of < 500/mm3 occurred in 19 (63%) patients. Weight loss occurred in only nine patients (median 3.4 kg, range 1.6-7.3). There was no difference between pre- and post-treatment weights (P=0.35). Two patients developed pulmonary embolism. Grade 3 or 4 non-hematologic toxicity occurred infrequently. This regimen appears to be similar in efficacy to the most active regimens reported by other investigators. Innovative features of the regimen include the brief treatment duration, the use of serial 7-day courses of filgrastim to facilitate weekly chemotherapy treatments, and the use of megestrol acetate to minimize constitutional symptoms. However the use of megestrol acetate in this setting may be associated with an increased risk of thromboembolic complications. This may provide a model for other palliative regimens specifically designed for patients with a favorable performance status and advanced NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appetite Stimulants; Carcinoma, Adenosquamous; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Lung Neoplasms; Male; Megestrol Acetate; Mesna; Middle Aged; Protective Agents; Recombinant Proteins; Survival Analysis; Treatment Outcome

Chemotherapy has not significantly altered the overall survival of patients with recurrent squamous cell carcinoma of the head and neck; therefore, the development of new agents is essential. The purpose of the current phase II study was to define the efficacy of ifosfamide in the treatment of recurrent squamous cell carcinoma of the head and neck. All patients were required to have squamous cell carcinoma of the head and neck that had recurred following surgery or radiotherapy or both. Patients may have received prior chemotherapy. Patients were initially treated with ifosfamide 2 g/m2/day for 4 days (dose level 0). Dose level-1 was 2 g/m2/day for 3 days, and dose level-2 was 2 g/m2/day for 2 days. All patients received mesna 400 mg/m2/day prior to and 1,200 mg/m2/day as a continuous infusion after ifosfamide. Thirty-eight patients were enrolled in the study. Five patients were inevaluable for toxicity or response. Overall, the regimen was well tolerated, with grade 4 granulocytopenia the only significant toxicity occurring in 16 patients. Overall, eight of 31 evaluable patients (25.8%) had a major response. Only one of the 10 patients (10%) with prior chemotherapy responded, but seven of the 21 patients (33.3%) with no prior chemotherapy had major responses. Ifosfamide is an active agent in recurrent squamous cell carcinoma of the head and neck. Further studies of ifosfamide in combination with other agents, particularly as induction therapy in patients with locally advanced disease, are warranted.

Topics: Adult; Aged; Agranulocytosis; Antineoplastic Agents, Alkylating; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Ifosfamide; Infusions, Intravenous; Injections, Intravenous; Male; Mesna; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Survival Rate

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

Mitomycin, ifosfamide, and cisplatin have demonstrated the best single-agent activity thus far in patients with non-small cell lung cancer (NSCLC), the most common malignant disease in the western world. For this reason, we initiated a phase II study, giving these three agents in combination (designated MIC) to 74 patients with inoperable NSCLC. Sixty-six patients were evaluable for response, of whom 30 (45%) demonstrated a partial response and 7 (11%) a complete response. These results, along with those obtained in two other phase II trials of MIC in NSCLC, promoted us to begin a large-scale, multicenter, phase III study of MIC in patients with inoperable limited-stage NSCLC. In this ongoing study, patients have been randomized to receive treatment with MIC and radiotherapy or radiotherapy alone. We hope to resolve the issue of whether a survival advantage is conferred on NSCLC patients treated with radiotherapy in combination with this promising chemotherapeutic regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Dexamethasone; Drug Administration Schedule; Furosemide; Humans; Ifosfamide; Lung Neoplasms; Mesna; Metoclopramide; Mitomycin; Mitomycins; Nausea; Neoplasm Staging; Vomiting

A total of 37 men with epidermoid head and neck cancer whose disease had recurred following primary treatment (surgery and/or radiotherapy) received first-line chemotherapy with ifosfamide at i.v. doses of 3 g/m2 given daily on 3 consecutive days in combination with mesna (600 mg/m2 x 3 oral daily doses on days 1-3) every 3 weeks. In all, 7 patients showed a partial response and 2 patients achieved a complete response, for an overall objective response rate of 26% (9 of 35 eligible patients; 95% confidence interval, 12.5%-43%). Excluding the 5 early nontoxic deaths observed during the first 3 weeks of therapy, the objective response rate was 30% (9 of 30 patients; 95% confidence interval, 15%-49.5%). Responses were seen in lung metastases (2 patients), lymph nodes (2 patients), skin (3 patients), and cases of local recurrence (5 patients). The median duration of responses was 3 months (range, 2-5 months). The main side effects of ifosfamide were alopecia (83% of patients), emesis (80%), granulocytopenia (23%), and mild mucositis (20%). Two poor-risk patients suffered severe CNS complications that were probably related to treatment. Three patients died due to chemotherapy-related complications (2 patients with CNS toxicity and 1 patient with granulocytopenic sepsis). In conclusion, ifosfamide appears to be an active drug in epidermoid head and neck cancer and merits further evaluation in this disease.

Topics: Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Ifosfamide; Male; Mesna; Middle Aged; Neoplasm Recurrence, Local

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

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

High-dose ifosfamide/mesna was administrated to 28 mostly pretreated patients with locally advanced and metastatic head and neck cancer who failed conventional surgery/radiation treatment. Primary sites include tongue (5), salivary gland (3), floor of mouth (5), oropharynx (2), hypopharynx (5) and larynx (8). The dose and schedule of ifosfamide (IF) was 3.5 g/m2 8 h, i.v. infusion, days 1-5, every 28 days, and mesna was given as 20% of IF dose intravenous bolus injection at 0, 2, 4, 6 and 8 h; mesna 40% of IF dose was given by oral route at 10 and 12 h, days 1-5, every 28 days. All patients were evaluable for both toxicity and response. 14 patients had received prior treatment with surgery plus radiation therapy and 14 patients radiation therapy. Following chemotherapy, 4 patients (14.2%) achieved complete remission and 8 patients (28.5%) achieved partial remission, with an overall response rate of 42.7%. Toxicity was reported for 186 cycles and ranged from mild to moderate: anemia 4, leukopenia 6, thrombopenia 1, nausea and vomiting 12, alopecia 28, microscopic hematuria 3, increased transaminase 1. No CNS symptoms and renal toxicity were registered. Median duration of survival is 11+ months (range 3+ to 18+ months). Nine patients died. We conclude that ifosfamide/mesna at this dose and schedule has a significant activity in recurrent head and neck cancer, and produces minimal toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Female; Head and Neck Neoplasms; Humans; Ifosfamide; Male; Mesna; Middle Aged

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

The protective effect of oral administration of the thiol compound sodium 2-mercaptoethane sulphonate (MESNA) against urothelial toxicity induced by ifosfamide (IF) was tested in a group of 45 patients with inoperable lung cancer under treatment with IF (2250 mg/m2 on days 2-5) as part of a polychemotherapy regimen repeated in a 4-week cycle. MESNA was given orally on the days of treatment with IF in 3 doses of 840 mg/m2, each administered at 0 hr (= injection of IF), 4 hr and 8 hr p.i. Out of a total of 88 courses of this treatment we observed 10 episodes of asymptomatic microscopic haematuria and no episodes of gross haematuria. In this group of 45 patients under protection with MESNA there were 5 complete remissions and 9 partial remissions (total 31%). A further group of 25 patients under polychemotherapy with IF were treated by conventional prophylactic measures (raised fluid intake and forced diuresis). In this group there were 1 complete and 5 partial remissions (total 24%), but nearly all patients developed either gross haematuria and/or symptoms of bladder irritation (cystitis and pollakisuria). There were no appreciable differences between the MESNA series and the conventional prophylaxis series with respect to either haematological or systemic toxicity of the cytostatic treatment. Our results support the view that MESNA, given orally in conjunction with combined cytostatic regimens which include IF, simplifies the treatment and provides optimum protection for the urinary epithelium. Protection with oral MESNA is particularly suitable for outpatients.

Topics: Administration, Oral; Adult; Aged; Carcinoma, Squamous Cell; Cyclophosphamide; Drug Therapy, Combination; Humans; Ifosfamide; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Middle Aged; Urinary Bladder Diseases

Injection of mesna into submucosal layers was recently reported to chemically soften connective tissue and facilitate the gastric endoscopic submucosal dissection (ESD) procedure. This study aimed to evaluate the safety and feasibility of similarly using mesna for esophageal ESD (mesna ESD).. We performed mesna ESD in 20 consecutive patients with superficial esophageal squamous cell carcinomas (SESCCs). To do this, a submucosal fluid cushion was initially formed using sodium hyaluronate, and the esophageal lesion was circumferentially isolated with a short blade needle-knife. Mesna solution was then injected into the submucosal layer, which was dissected mechanically by cleavage using the tip of a cap-fitted endoscope. The number of electrosurgical incisions was recorded by computer software in real time. The data from 20 conventional ESD procedures without mesna (consecutive 10 SESCCs pre and post the 20 consecutive mesna ESD) were used for comparison to evaluate the mesna ESD.. The mesna ESDs achieved en bloc and R0 resection success rates of 100 and 95 %, respectively. There was no perforation or uncontrollable hemorrhage during and after mesna ESD, and the median procedural time of submucosal dissection was significantly less with mesna ESD than with conventional ESD (median; 8 vs. 15 min, P < 0.05). There were also significantly fewer electrosurgical incisions made during the mesna ESD than with conventional ESDs (median; 65 vs. 183 times, P < 0.01).. Mesna ESD for SESCCs is a safe procedure with the potential to facilitate esophageal ESD.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Dissection; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagoscopy; Esophagus; Expectorants; Feasibility Studies; Female; Humans; Injections; Male; Mesna; Middle Aged; Mucous Membrane; Prospective Studies; Treatment Outcome

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Clinical Trials, Phase II as Topic; Data Interpretation, Statistical; Endpoint Determination; Head and Neck Neoplasms; Humans; Ifosfamide; Mesna; Neutropenia; Paclitaxel; Reproducibility of Results; Survival; Taxoids

Generalized and partial seizures with secondary generalization were observed during ifosfamide-mesna (IFO) treatment in a patient with lung epidermoid carcinoma. Seizures appeared in a stereotyped manner on the 3rd of the 4th and 6th day of treatment with IFO. Partially resolutive confusion was observed after the last cure. Brain CTS were normal. The responsibility of IFO is considered in the development of these neurological toxic manifestations.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Epilepsy; Fatal Outcome; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Seizures

Ifosfamide has shown promising single-agent activity in non-small cell lung cancer (NSCLC). We combined ifosfamide (1,800 mg/m2 plus mesna 1,100 mg/m2 by intravenous [IV] continuous infusion daily for 3 days) with cisplatin (20 mg/m2 IV for 3 days) and etoposide (80 mg/m2 IV for 3 days) and treated 41 chemotherapy-naive patients with recurrent or metastatic NSCLC. Fifteen (40.5%) of the 37 evaluable patients had objective responses (1 complete and 14 partial). Patients with good performance status (Zubrod scale 0 or 1) had a higher response rate than the patients with poor performance status (Zubrod scale 2) (11 of 21 patients [52.4%] versus four of 16 [25.0%]), but the difference was not statistically significant (P = .09). Median survival has not been reached, with 17 patients still alive after a median follow-up of 39 weeks (range, 21 to 56). Significant myelosuppression occurred, with granulocytopenia being the dose-limiting toxicity. Overall, treatment was well tolerated. Considering the pooled response rate of 32% with cisplatin/etoposide regimens and the previous experience from our institution, the results with this three-drug regimen are very encouraging, and its further investigation is warranted.

Topics: Adenocarcinoma; Adult; Aged; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Clinical Protocols; Clinical Trials, Phase II as Topic; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Remission Induction; Survival Rate

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

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

Seventeen patients with advanced epidermoid carcinoma of the esophagus were treated with ifosfamide (IFOS) 1.5 mg/m2/day intravenously on days 1-5 every 28 days. Mesna was given concurrently at 20% of the IFOS dose prior to and 4 and 8 h after IFOS for uroprotection. Toxicity in this trial was severe since life-threatening leukopenia occurred in one patient, Grade 3 nausea and vomiting (necessitating termination of treatment) in two patients, and Grade 3 neurotoxicity (cerebellar dysfunction) in two patients. Two patients developed severe infections (Grade 3). Only four patients experienced no toxicity. One patient had a partial response with a response duration of 8 weeks. The median survival of all patients is 10 weeks. It is concluded that IFOS as given in this trial has limited activity in esophagus carcinoma with severe toxicity.

Topics: Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Evaluation; Esophageal Neoplasms; Female; Humans; Ifosfamide; Male; Mesna; Middle Aged

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