Phase II trial of ifosfamide and mesna in advanced ovarian carcinoma: a Gynecologic Oncology Group Study

Ifosfamide (isophosphamide) and mesna (2-mercaptoethane sodium sulfonate) were administered intravenously at monthly intervals to 46 patients with advanced epithelial ovarian carcinoma refractory to or recurrent after cisplatin-containing combination chemotherapy. Initially, ifosfamide was given as 1.5 g/m2/d x 5 days and mesna as 300 mg/m2 every 4 hours for three doses following ifosfamide, but the initial dose of ifosfamide was reduced to 1.2 g/m2 because of toxicity. Four of the patients initially entered were found to be ineligible: two who had had more than one prior chemotherapy regimen and two who did not have ovarian primaries. One patient received an inadequate trial and four patients had discontinuation of therapy because of toxicity, leaving 41 evaluable for response. Three patients (7.0%) had complete responses and five (13.0%) had partial responses for an overall response rate of 20.0%. Response duration ranged from 2.1 to 20.3 + months with a median of 6.9 + months. Two patients died of renal failure, one of whom had no known renal disease and received 1.5 g/m2/d x 5 days ifosfamide. The second patient received the 1.2 g/m2 dose and was found to have chronic pyelonephritis and pyonephrosis at autopsy. Gynecologic Oncology Group (GOG) grade 3 or 4 granulocytopenia was seen in eight (19.5%), grade 3 or 4 thrombocytopenia in four (9.8%), and grade 3 or 4 neurotoxicity in six (14.6%) of the 41 patients evaluable for toxicity. Ifosfamide/mesna is active in epithelial ovarian cancer. GOG trials in untreated patients are being initiated and toxicity is being evaluated.     

Ifosfamide, methotrexate, and 5-fluorouracil: effective combination in resistant breast cancer

Ifosfamide has definite efficacy in many malignant tumours, including breast cancer. In the present study we substituted cyclophosphamide with ifosfamide in the combination CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) regimen in 25 patients with breast cancer whose disease was refractory to CMF or who had relapsed after previous response. Ifosfamide was given in an i.v. infusion at a dose of 1.2 g/m² daily for 5 days, together with mesna as a uroprotector (at 20% of the ifosfamide dose). Methotrexate was given at a dose of 40 mg/m² and 5-fluorouracil was given at 600 mg/m², both by i.v. push. Courses were repeated every 21 days. The 24 evaluable patients received 3–12 courses (average, 5 courses); results included a complete remission in 3 patients (12.5%) and a partial remission in 3 (12.5%). Among the remaining patients, improvement was seen in 4 (16.6%); stable disease, in 7; and progressive disease, in 7 (29.2%). The complete responses lasted for 11+, 13+, and 15+ months, and partial remissions, for 2, 6, and 9 months. The responses were detected in soft-tissue as well as visceral lesions, but not in bony lesions. The responders remain under follow-up. This study shows the efficacy of ifosfamide-containing chemotherapy in breast cancer. As toxicities were tolerable, higher doses of ifosfamide could safely be used in these patients. Use of this combination as first-line therapy in breast cancer could be considered for a future study.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

Ifosfamide with and without Adriamycin in advanced uterine leiomyosarcoma

Uterine leiomyosarcomas are rare tumours and the results of treatment of advanced disease are poor. Ifosfamide and Adriamycin are both known to be active drugs in soft-tissue sarcomas. We present our experience using ifosfamide alone and in combination with adriamycin in advanced or recurrent uterine leiomyosarcomas. Ifosfamide alone was given as a 24-h infusion at doses ranging from 5 to 7.5 g/m², with mesna rescue. In the combination regimen, ifosfamide was given at a dose of 5 g/m² and Adriamycin, at a dose of 40 or 60 mg/m². Ten patients were treated with ifosfamide alone, with only one partial response lasting 6 months. In all, 11 patients were treated with ifosfamide and Adriamycin, which resulted in 1 complete response that lasted 11 months. Although many of the patients had extensive disease and some had undergone prior treatment with other chemotherapy, ifosfamide would appear to have only modest activity at the dose and schedule used.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

Treatment of metastatic breast cancer with the combination of ifosfamide, epirubicin and 5-fluorouracil

An ongoing trial of combination chemotherapy using ifosfamide (Holoxan), epirubicin and 5-fluorouracil was started in 1987. A total of 30 patients with metastatic cancer of the breast received 1.5 g/m² i. v. ifosfamide over 60 min on days 1–3, 50 mg/m² i. v. epirubicin on day 1 and 500 mg/m² i. v. 5-fluorouracil on day 1, followed by mesna (Uromitexan) given at 20% of the ifosfamide dose at 0, 4 and 8 h. The courses were repeated every 4 weeks. In all, 198 courses were given, ranging from 3 to 13 (median, 7) cycles/patient. The mean age of the 30 patients was 48 years (range, 35–66 years); 5 had not previously received chemotherapy and the others had failed prior cytotoxic and endocrine therapy. Overall, 28 patients were evaluable, 7 (25%) showed a complete response and 15 (54%) had a partial response, for an overall response rate of 22/28 (79%). Three patients showed stable disease with improved symptoms, and in three cases disease progression occurred. The median duration of response was 9 months (range, 3–20 months). Median survival was 11 months for all patients, 15 months for CRs, 10 months for PRs, 6 months for stable disease and 12 months for progressive disease (PD). Survival for the 22 responding patients was 12 months. Toxicity was acceptable and included alopecia, mucositis, nausea, vomiting, diarrhoea, mild cystitis and myelosuppression. Epirubicin did not appear to produce cardiac toxicity, and ifosfamide with mesna did not seem to result in severe urotoxicity. Chemotherapy with ifosfamide, epirubicin and 5-fluorouracil proved to be effective for treatment of advanced breast cancer and should be further studied in large, controlled trials.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

A phase II study of ifosfamide in endometrial cancer

Around 32% of all patients with endometrial carcinoma relapse after primary therapy. The outlook for these patients is poor. Ifosfamide (IFX) has activity in a number of gynaecological malignancies and was selected for evaluation in this disease. The aims of this study were to assess the activity and toxicity of IFX in recurrent endometrial carcinoma no longer amenable to radical local treatment. In all, 16 evaluable patients with symptomatic advanced metastatic or recurrent disease entered a phase II study of this drug. Patients received IFX (5 g/m²) as a 24-h infusion, with mesna (8 g/m²) given during and for 12 h following IFX to prevent urothelial toxicity. Treatment was repeated every 21 days. Two patients showed evidence of response [one complete response (CR) of 3 months and one partial response (PR) lasting 5 months]. Most patients experienced nausea and vomiting, and WHO grade 3/4 alopecia invariably occurred after two or more cycles. Four patients developed severe (grade 3/4) IFX/mesna CNS toxicity, and four other patients had mild (grade 1/2) CNS toxicity. Significant myelosuppression was seen in 3/41 cycles. Haematuria was uncommon and invariably mild. There were two toxic deaths (one due to grade 4 CNS toxicity and one due to septicaemia). IFX has activity in endometrial carcinoma, but responses are of limited duration and toxicity is considerable.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

A randomised study of carboplatin vs sequential ifosfamide/carboplatin for patients with FIGO stage III epithelial ovarian carcinoma. The London Gynaecologic Oncology Group.

In a study designed to compare response rates of patients with stage III epithelial ovarian carcinoma to ifosfamide and carboplatin, 152 patients were randomised to receive either sequential therapy with three cycles of ifosfamide followed by three cycles of carboplatin, or to six cycles of single agent carboplatin. Ifosfamide was given every 3 weeks in a dose of 5 gm m-2 as a 24 h infusion with mesna, 1 gm m-2 by i.v. bolus prior to ifosfamide, 3 gm m-2 with ifosfamide, and 1 gm m-2 as an 8 h infusion after ifosfamide. Carboplatin was given in a dose of 400 mg m-2 by short i.v. infusion every 4 weeks. Sixty-eight evaluable patients were randomised to sequential ifosfamide/carboplatin, and 67 to single agent carboplatin. Median follow-up is 36 months (range 5.5-82.3). After three cycles of treatment two patients in the ifosfamide/carboplatin arm achieved complete remission (CR), and 12 partial remission (PR) for an overall response rate of 29%, whereas in the carboplatin arm ten patients achieved CR, and 23 PR, for an overall response rate of 63% (P = 0.0008). Seven of 15 patients with progressive disease, and nine of 20 patients with stable disease at the initial response evaluation, following three cycles of ifosfamide, subsequently responded to carboplatin therapy so that the final response rate to the complete regimen was 65% for the ifosfamide/carboplatin arm, compared to 71% for the carboplatin arm (NS). For the ifosfamide/carboplatin arm, median recurrence free survival and overall survival were 14.1 months and 18.7 months. Corresponding figures for the carboplatin arm were 14.5 months and 21.5 months (NS). Both treatments were generally well tolerated. However 47% of patients in the ifosfamide/carboplatin arm developed alopecia sufficient to require a wig, compared to only 2% in the carboplatin arm. Ifosfamide is clearly less effective, and more toxic than carboplatin. Ifosfamide failures can however be effectively salvaged by subsequent carboplatin treatment. Ifosfamide cannot be recommended for single agent therapy in ovarian carcinoma, however the combination of carboplatin plus ifosfamide might be a suitable treatment to be tested in a future randomised study against carboplatin alone.     

Ifosfamide/etoposide and mesna uroprotection in advanced breast cancer

The object of the study was to evaluate the effectiveness of ifosfamide/etoposide and mesna therapy in advanced breast cancer. A total of 44 patients with breast cancer were included in the trial. Eligibility criteria included measurable, refractory disease; prior anthracycline therapy (or its contraindication); a life expectancy of at least 3 months; and adequate hepatic, renal, CNS and bone marrow function. All patients were70 years of age and had a Karnofsky performance status of50%. There were 36 evaluable cases. Sites of metastatic disease included bone (19), skin (18), liver (9), lung (14), lymph node (19), and miscellaneous (7). Treatment consisted of 1,500 mg/m² ifosfamide given i.v. on days 1–5, 120 mg/m² etoposide given i.v. on days 1–3, and 400 mg i.v. mesna given with and at 4 and 8 h after ifosfamide. Cycles were repeated every 28 days. Initial doses were reduced by 25% or 50% in patients who had previously undergone both chemotherapy and radiotherapy. A median of 4 cycles (range, 2–8) were given. The myelotoxicity was marked: WHO grades 3/4 leukopenia (n=37), grades 3/4 thrombocytopenia (n=12), and grades 2/3 anemia (n=13). Due to myelotoxicity, dose reduction or prolongation of treatment-free intervals was necessary in 28 cases. Alopecia was seen in 35 patients and CNS toxicity, in 8. Partial remission (PR) was obtained in five cases and complete remission (CR), in three. Sites of response included the lung (5), skin (4), lymph node (5), and peritoneum (1). The duration of response was 4 (n=2) and 8 (n=1) months for CR and 2 (n=2), 6 (n=2), and 10 (n=1) months for PR. We conclude that the ifosfamide/etoposide and mesna regimen is effective, but its myelotoxicity is treatment-limiting.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

Ambulatory administration of 5-day infusion ifosfamide + mesna: a pilot study in sarcoma patients

Purpose

Ifosfamide is a cornerstone of chemotherapy in bone and soft-tissue sarcoma. Results of pharmacokinetic studies indicate that the optimal schedule of ifosfamide should be repeated doses over several days. With the development of 5-day infusion devices, we developed and evaluated a 5-day infusion regimen of ifosfamide in sarcoma patients in the outpatient setting.

Methods

Sarcoma patients requiring chemotherapy after at least one doxorubicin-based line were enrolled in this study. Ifosfamide + mesna was administered as 1:1 concentration for a total of 6 g/m² of each over 5 days (i.e. 1.2 g/m² per day as continuous infusion) every 3 weeks. Patients were treated until progression or limiting toxicity, and salvage surgery was attempted when possible. An economic study was run comparing ifosfamide plus mesna as a 5-day infusion regimen and conventional Ifosfamide regimen.

Results

Thirteen sarcoma patients were evaluable. The median number of cycles per patient was 6 (range, 1–8), for a total of 69 cycles. No acute encephalopathy or aggravation of renal function was noted. Acute grade 3 and 4 haematological toxicities were observed in 11.6 and 1.4% of patients, respectively without febrile neutropenia. Median time to progression survival and overall survival were 8.7 and 21.5 months, respectively. Total cost per cycle for a 2-m² patient body surface area was ambulatory infusion = 1,891 € and conventional ifosfamide = 6,256 €.

Conclusion

The combination of ifosfamide and mesna as a continuous infusion over 5 days is feasible and well tolerated in the outpatient setting using infusion device. Its very favourable cost-effectiveness invites to further develop this approach.     

A phase II study of ifosfamide and cisplatin chemotherapy for metastatic or relapsed carcinoma of the cervix

Summary A total of 44 women received a combination of ifosfamide (1.5 g/m² daily x5) and cisplatin (50 mg/m² on day 1 only) as first-line chemotherapy for recurrent or metastatic carcinoma of the cervix. In all, 12/42 (38%) evaluable patients responded, with the median duration of response being 7 months. Bone marrow and gastrointestinal toxicity were frequently severe. There were 3 septic death. Although cisplatin plus ifosfamide is an active combination against this disease, these results suggest that it is no more so than either drug used alone.The London Gynaecology Oncology Group (LGOG) comprising the Departments of Medical Oncology     

Phase II study of carboplatin/ifosfamide in untreated advanced cervical cancer

A total of 32 patients with advanced squamous-cell carcinoma of the cervix were treated with 300 mg/m² i. v. carboplatin and 5 g/m² ifosfamide as a 24-h i. v. infusion, both given on day 1 every 4 weeks. In all, 3 (9%) complete responses (CRs) and 19 (59%) objective responses (CR+PR) were achieved in 32 patients. Myelosuppression with leukopenia and/or thrombocytopenia of WHO grade 4 in 28% and 13% of patients, respectively, was the main toxicity. The results of our study suggest that carboplatin/ifosfamide is active as neoadjuvant treatment in advanced cervical cancer.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

Ifosfamide given as a 24-h infusion with mesna in patients with recurrent ovarian cancer: preliminary results

The continuous 24-h infusion of ifosfamide (IFX) with mesna was studied in 44 patients with therapyresistant or relapsing ovarian cancer. All patients had stage III disease and had been pretreated with at least one combination comprising an alkylating agent and a cisplatin analogue (22, with one combination; 16, with two; and 6, with three or more). The median number of IFX cycles received was two. Of 40 evaluable patients, 2 achieved a complete response, 5 showed a partial response and 6 had stable disease. A total of 27 patients had tumor progression after one or two treatment cycles. All seven responders had responded to previous treatment for a median duration of 5 months (range, 5–41 months). No patient who progressed during alkylating-agent treatment responded to IFX given subsequently. The median progression-free period was 6 months (range, 4–12 months), and the median overall survival was only 6 months, indicating the advanced stage of disease in these patients. The median overall survival in progressive patients was 5 months (range 2–13+months) and that in the remaining group was 13 months (ranges 3⁺-24 months) (P<0.05). this=" treatment=" was=" moderately=" well=" tolerated.=" grade=" 3=" nausea=" and=" vomiting=" occurred=" in=" 27%=" of=" cycles=" and=" grade=" 3-4=" leukopenia=" was=" observed=" in=" 47%,=" but=" thrombocytopenia=" was=" hardly=" ever=" found.=" in=" eight=" patients=" there=" was=" a=" deterioration=" of=" renal=" function.=" among=" a=" total=" of=" 131=" cycles,=" the=" dose=" was=" reduced=" for=" only=" 9=" due=" to=" myelotoxicity=" and=" for=" 3=" due=" to=" nephrotoxicity.=" ifx=" seems=" to=" be=" active=" only=" in=" patients=" who=" have=" relapsed=" after=" responding=" to=" previous=" cytotoxic=">Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

High-dose ifosfamide and mesna in advanced breast cancer A phase II study

Thirty-two patients with metastatic breast cancer had previously been treated with chemotherapy (in cluding anthracyclines). They were included in a trial to receive 6 g/m³ ifosfamide, mixed with 6 g/m² mesna in 1000 ml saline infusion, infused over 4 h. Therapy was repeated every 21 days; the dose was reduced by 50%. Twenty-eight patients could be evaluated. An average of 4.2 cycles (range 2–8) was applied. One patient (4%) showed complete remission. Ten patients (36%) had a partial response. Ten patients (36%) experienced SD and the remaining patients (25%) PD. We conclude that high-dose ifosfamide shows activity in this group of pretreated patients and merits further investigation.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursin, London, September 3–7, 1989     

A phase II study of ifosfamide/mesna with doxorubicin for adult soft tissue sarcoma

Summary In a phase II study, 16 adult patients with locally advanced or metastatic soft tissue sarcomas were treated with i.v. infusions of ifosfamide/mesna 5 g/m² plus i.v. doxorubicin 40 mg/m². Courses were given every 3 weeks up to a maximum of six courses in responding patients. Six patients (37.5%) had either complete (1 patient) or partial responses (5 patients). Confidence limits for this response rate were 15.2%–64.5% (95% confidence level). There was one toxic death in association with encephalopathy, renal and bone marrow failure. Unilateral pneumothoraces occurred in 2 patients with large pulmonary metastases. Recurrent severe ifosfamide/mesna encephalopathy occurred in 2 patients at risk for this complication; patients who develop severe ifosfamide/mesna encephalopathy should not be retreated with this drug. Ifosfamide/mesna with doxorubicin is an active combination to treat adult soft tissue sarcoma but, despite the feasibility of the combination, sequential monotherapy with these drugs might provide similar or better clinical benefit.     

Cisplatin-ifosfamide as neoadjuvant chemotherapy in stage IIIB cervical uterine squamous-cell carcinoma

Survival in patients with advanced cervical cancer (stage III B) treated by radical radiotherapy is low. In this study we attempted to assess the efficacy of thecis-diamminedichloroplatinum(II) (CDDP)-ifosfamide combination as neoadjuvant chemotherapy in advanced cervical cancer. The treatment schedule was: 20 mg/m² CDDP on days 1–5; 1.5 g/m² ifosfamide on days 1–5; and 900 mg/m² mesna on days 1–5. Courses were given every 28 days. Radiotherapy was given 15 days after the completion of chemotherapy. A total of 26 patients were entered in this trial. Of the 24 patients evaluable for response, 15 (62.5%) achieved at least a 50% reduction in tumor volume, 6 (25%) showed stable disease, and three (12.5%) had progressive disease. At 38 months (mean follow-up) after completion of radiotherapy, 13 of the 24 (54%) evaluable patients were disease-free; 73% of the patients responding to chemotherapy vs 22% of the nonresponders remained free of disease (Fisher's exact test:P<0.02). major=" hematologic=" depression=" occurred=" in=" 2=" of=" the=" 26=" patients=" evaluable=" for=" toxicity.=" no=" cns=" toxicity=" was=" detected.=" these=" results=" are=" superior=" to=" those=" obtained=" by=" radical=" radiotherapy=" alone.=" future=" treatment=" should=" be=" directed=" toward=" improving=" response=" rates=" as=" the=" best=" way=" of=" increasing=" both=" local=" and=" distant=" long-term=" disease=" control=" in=" these=">Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

Ifosfamide and mesna: marginally active in patients with advanced carcinoma of the pancreas

Ifosfamide, an analogue of cyclophosphamide, has therapeutic activity against a wide variety of human malignancies. In a phase II trial in carcinoma of the pancreas, we treated 31 patients who had not received prior chemotherapy with a median ifosfamide dose of 2 g/m2/d (range, 1.5 to 2 g/m2/d) administered intravenously (IV) over one hour for five consecutive days every 3 weeks. 2-mercaptoethane sulphonate (mesna), an acrolein antagonist with known uroendothelial protective properties, was administered IV at a dose of 400 mg/m2 over 15 minutes before the daily dose of ifosfamide and repeated every four hours for two additional doses. Among 30 evaluable patients, one patient achieved a complete remission (26+ months) and another patient had a partial remission (4 months). The median duration of survival of all patients from the start of ifosfamide therapy was only 3 months (range, 1 to 26+ months). Treatments were generally well tolerated. The most common toxic effects included granulocytopenia, nausea and vomiting, malaise, anorexia, and mild hematuria. Mesna offers an adequate protection against uroendothelial injury caused by ifosfamide. Despite the previously reported response rate of greater than 20% at the same or lower doses of ifosfamide in other studies, our data suggest that ifosfamide is only marginally active against cancer of the pancreas and appears to be of minimal value in the treatment of patients with this tumor.     

Dose intensity of carboplatin in combination with cyclophosphamide or ifosfamide

In two separate studies of patients with ovarian cancer, subjects were treated on a protocol comprising 400 mg/m² carboplatin in combination with 1 g/m² cyclophosphamide (group A) or 5 g/m² ifosfamide with mesna (group B). The dose intensities achieved in group A were 87.2 mg/m² carboplatin per week and 245.8 mg/m² cyclophosphamide per week (34 patients). In group B, the dose intensities achieved were 124.1 mg/m² carboplatin per week and 2,020 mg/m² ifosfamide per week (25 patients). Two formulae for the prediction of the optimal dose of carboplatin based on renald function and degree of myelosuppression are compared with that based on surface area, and that recently proposed by Calvert is recommended. The importance of dose intensity and the total dose delivered in phase II and III studies is emphasized.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, Septemberd 3–7, 1989     

A phase II evaluation of ifosfamide and mesna in unresectable diffuse malignant mesothelioma. A Southwest Oncology Group study.

BACKGROUND. Malignant mesothelioma is a highly treatment-resistant neoplasm. This study represents an attempt to define an effective form of systemic therapy. METHODS. Twenty-six patients with unresectable diffuse malignant mesothelioma were enrolled in Southwest Oncology Group (SWOG) study 8731 and treated with ifosfamide, 2 g/m2 intravenously for 4 days, and mesna 2 g/m2 intravenously for 5 days, every 3 weeks. Patients were either previously untreated with chemotherapy or had at most one prior systemic treatment. RESULTS. Two patients, or 8% (95% confidence interval, 1-25%), achieved partial response, with response durations of 4 and 6 months. One additional patient met criteria for tumor size reduction but not duration criteria. Thirteen (50%) patients had stable disease of 4 months' median duration (range, 1-13 months). The median survival of the entire group was 6.5 months. The dose-limiting toxicity was granulocytopenia (11 patients, < or = 250/microliters). CONCLUSIONS. Ifosfamide/mesna has modest activity in malignant mesothelioma. It could be tested using alternate dosage schedules and in combination with other agents in treating this highly resistant neoplasm.     

Chemotherapy with high dose ifosfamide/mesna plus cisplatin for the treatment of ovarian cancer: a study of the Grupo de Estudio y Tratamiento Latino-Americano del Cancer

Twenty-one evaluable patients with FIGO stages II-IV epithelial ovarian cancer, median age 57 (range 47-75 years), were treated with ifosfamide (IF), 3 g/m2 diluted in 500 ml saline solution, 8 hour intravenous (i.v.) infusion on days 1-5; mesna 20% of IF dose, i.v. bolus injection, was given at hours 0 and 4; mesna 40% of IF dose by oral route at hours 8 and 12, days 1-5; plus cisplatin 20 mg/m2 diluted in 500 ml saline solution, 2 hour i.v. infusion, days 1-5. Cycles were repeated every 4 weeks. All patients had metastatic lesions (mesentery, pleura, colon, cervix, abdominal wall, lung, liver, bladder, and nodes). Toxicity ranged from mild to moderate. All patients experienced alopecia, nausea, and vomiting. Neutropenia and anemia ranged from mild to moderate. One patient experienced mild brain confusion and two patients microscopic hematuria. Ten clinically complete responses (47%) and five clinically partial responses (23%) were registered, for an overall 70% objective response. However, after a second look performance in 10 patients with clinically complete response, six of 10 patients showed a pathological complete response and four showed pathological partial response. The median duration of complete response is about 33 months, and median partial response duration is 14 months. Although the numbers are small, these data indicate that combination chemotherapy with high dose ifosfamide/mesna plus cisplatin may be an active treatment for advanced ovarian carcinoma.     

Epirubicin and ifosfamide in patients with refractory breast cancer and other metastatic solid tumours

The combination of ifosfamide (IFO) and epirubicin (EPI) has been found to be an effective regimen in the treatment of metastatic tumours and shows remarkable activity in heavily pretreated breast cancer patients. A combination of EPI (35 mg/m² on days 1 and 2) and IFO (1.8–2.5 g/m² on days 1–5) was given to 58 patients with refractory breast cancer (n=23), metastatic sarcomas (n=15) and other solid tumours (n=20). Due to extensive prior therapy, the IFO dose had to be adapted to the individual haematological situation. In all, 55 patients were evaluable; we observed 5 complete (CRs) and 16 partial responses (PRs). In addition, 18 patients experienced a minor response (MR) or no change (NC). The median duration of all responses was 6.7 months. Toxicity was generally mild and closely related to previous therapy.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

Ifosfamide with mesna uroprotection in the management of lung cancer

Fourteen patients with extensive disease small cell bronchogenic carcinoma (SCBC) received ifosfamide at 2,000 mg/m2/day for 5 consecutive days with simultaneous mesna and vincristine while 26 patients with extensive disease non-small-cell bronchogenic carcinoma (N-SCBC) received the same regimen without vincristine. Eight partial responses (57%) were observed with a 40-week median survival in the case of SCBC and four partial remissions (15%) with a 31-week median survival in N-SCBC. Granulocytopenia was the dose-limiting toxicity, whereas urotoxicity was well controlled with mesna. Neuropsychiatric toxicity consisted of anxiety, agitation, confusion, and hallucination. Neurobehavioral testing detected worsened performance during ifosfamide treatment. Ifosfamide is one of the few active agents in N-SCBC.