mesna and Pancreatic-Neoplasms

The Italian Oncology Group for Clinical Research (GOIRC) randomized 55 naive patients with advanced pancreatic cancer (APC) between intravenous fluorouracil (5FU) 400 mg/m2, days 1-5 and folinic acid (FA) 200 mg/m2, days 1-5 alone, using Machover's schedule, or with FU, FA, and ifosfamide (IFO) 5 g/m2, day 1 and Mesna. In both arms, treatment was repeated every 28 days. Fifty-one patients were evaluable for response. The overall response rate was 6% (3 out of 51), 1 out of 29 (3%) complete response (CR) in the arm with FU plus FA, and 2 out of 22 (9%) partial responses (PR) in the arm with IFO. The duration of response rate was 39, 55, and 74 weeks, respectively. Median survival time was 21 weeks (range, 4-83 weeks) for 5FU/FA and 16 weeks (range, 3-106 weeks) for the FU/FA/IFO arm. Diarrhea, mucositis, and vomiting occurred in the majority of patients. One patient died due to toxicity. The combination of 5FU plus FA failed to demonstrate therapeutic activity in patients with APC and was associated with moderate to severe toxicity that could lower the quality of life of these patients. Ifosfamide did not potentiate the activity of this combination. Neither of these combinations should be considered for treatment of patients with APC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Fluorouracil; Humans; Ifosfamide; Leucovorin; Male; Mesna; Middle Aged; Pancreatic Neoplasms

Phase II studies on ifosfamide and mesna in pancreatic cancer have mostly been inconclusive. In all of these studies ifosfamide was administered as an i.v. bolus or by short infusions. Since dose fractionation of ifosfamide over several days increases its therapeutic index, we chose to maximize the dose fractioning by selecting a continuous-infusion schedule (1.75 g/m2 on days 1-5 every 21-28 days, with mesna 60%-100% of the ifosfamide dose up to 12 h after ifosfamide). Since 1987 29 patients (performance status less than or equal to 2) with advanced inoperable adenocarcinoma of the pancreas were studied (8 women and 21 men; median age 58 years: 36-73 years). A total of 25 patients are evaluable for response (1 ineligible; 3 inevaluable: 2 early deaths due to disseminated intravascular coagulation, 1 refusal). One female patient with a complete response on computed tomography scan (after five cycles) but residual liver metastases on surgical exploration survived for 473 days. Three male patients with partial response survived for 205, 335 and 355 days. Six more patients with minor response (3) or no change (3) but significant decrease of tumour marker CA 19-9 had a median survival of 213 days (106-243). Responders seemed to benefit in terms of pain relief and general well-being. The median overall survival of all patients was 148 days (21-473). Haematotoxicity was rarely dose-limiting [median nadirs: white blood cells = 2.1 x 10(9)/l (0.45-6.4), Hb = 10.7 g/dl (7.5-13), platelets = 137 x 10(9)/l (21-411)]. Nausea and vomiting were mild with prophylactic oral metoclopramide. No central nervous system toxicity or urotoxicity was observed. Alopecia was seen in all patients who had received at least two cycles. Continuous infusion of ifosfamide was generally well tolerated and useful for palliation in 10 of 25 patients. A higher dose intensity is recommended.

Topics: Adenocarcinoma; Adult; Aged; Drug Administration Schedule; Drug Evaluation; Female; Humans; Ifosfamide; Infusions, Intravenous; Male; Mesna; Middle Aged; Pancreatic Neoplasms; Remission Induction

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.

Topics: Adult; Aged; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Ifosfamide; Male; Mercaptoethanol; Mesna; Middle Aged; Pancreatic Neoplasms

Small cell carcinoma of the pancreas is a very rare malignancy with 18 cases reported in the literature, of which only 3 were treated with chemotherapy. A 52-year-old man was diagnosed with small cell carcinoma originating in the head of the pancreas and invading the duodenum. He was treated with a similar approach as for localized small cell lung cancer, with six cycles of combination chemotherapy and local radiotherapy, and went into complete remission. After 3 months, he developed liver metastases along with an enlarged left supraclavicular lymph node. He was treated with two cycles of CVA, but developed lung metastases and was treated with ifosfamide/mesna. However, his overall condition deteriorated and hospice care was instituted until the patient's demise. The patient survived 14 months following diagnosis, significantly longer than the 15 reported patients with small cell pancreatic carcinomas not treated with chemotherapy. Combination chemotherapy and radiation therapy as it is utilized for small cell lung cancer appear to be beneficial for small cell carcinoma of the pancreas.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Duodenal Neoplasms; Fatal Outcome; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Pancreatic Neoplasms; Radiotherapy Dosage; Tomography, X-Ray Computed; Vincristine

The oxazaphosphorine prodrug Ifosfamide (IFO) in conjunction with the uroprotective agent Mesna is becoming a standard alkylating agent. It has an increased therapeutic index when given as a fractionated dosage over 3-5 days. Maximal fractionation is achieved by continuous infusion over several days and has been shown to be less emetic and neurotoxic than regimens with bolus infusions. We have studied in patients with advanced cancer the feasibility and bioavailability of a subcutaneously administered isotonic and neutral (pH 7) IFO solution given continuously over 10 h for up to 5 days. A portable disposable gas-driven infusor syringe was used. Our results show 90-100% bioavailability of sc administered IFO. The isotonic solution of IFO (pH 7) showed no significant local toxicity during or after sc administration. Haematotoxicity was equal for sc and iv application. No uro- or neurotoxicity has been observed in 24 sc cycles. We conclude that this novel continuous sc IFO infusion over several days is a rational, well-tolerated and economical way of delivering this drug on an outpatient basis.

Topics: Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Biological Availability; Drug Administration Schedule; Feasibility Studies; Female; Humans; Hydrogen-Ion Concentration; Ifosfamide; Infusion Pumps, Implantable; Infusions, Intravenous; Injections, Subcutaneous; Male; Mesna; Middle Aged; Pancreatic Neoplasms; Sarcoma; Soft Tissue Neoplasms

The Gastrointestinal Tumor Study Group (GITSG) investigated the efficacy of ifosfamide with mesna uroprotection in 30 patients with advanced inoperable pancreatic carcinoma that was confirmed histologically. All patients were required to have at least one bidimensional measurable lesion that could be followed by palpation or radiologic examination. Genitourinary toxicity presenting as hematuria occurred in five patients, but was not severe enough to curtail treatment in any of these patients. The major toxicity was neurologic, with 12 patients (41%) reporting at least one episode; four of which were graded as severe and two as fatal. Three partial tumor responses to treatment were reported (10%) and the median survival time was just 11 weeks. In our experience, ifosfamide with mesna uroprotection does not appear to be active in pancreatic carcinoma.

Topics: Adult; Aged; Carcinoma; Drug Evaluation; Female; Hematuria; Humans; Ifosfamide; Male; Mesna; Nervous System Diseases; Pancreatic Neoplasms

Ifosfamide was studied in advanced pancreatic tumor at the National Cancer Institute, Cairo. Over five years, 25 patients received a daily dose of 1.8 g ifosfamide for five days, courses reported every 21 days. Complete remission was achieved in 1 patient and partial remission in 14 patients, an overall result of 60%, average duration of response being 12+ months. Mesna was used for uroprotection.

Topics: Adult; Alopecia; Anemia; Drug Evaluation; Female; Humans; Ifosfamide; Leukopenia; Male; Mesna; Middle Aged; Pancreatic Neoplasms