mesna and Lung-Neoplasms

Soft tissue sarcomas comprise a heterogeneous group of malignancies of mesenchymal origin. Although sarcomas can arise virtually anywhere, the most common primary site is the extremity. The development of metastatic disease poses a major clinical problem because it is seldom amenable to a curative treatment. However, with careful and expert multidisciplinary team selection of patients with metastatic sarcoma-balancing probability of benefit with certain toxicity-a combined multimodality approach may provide hope to a select few for prolonged survival and even cure.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dacarbazine; Doxorubicin; Humans; Ifosfamide; Lung Neoplasms; Mesna; Sarcoma; Treatment Outcome

We present the second reported case of a myxoid liposarcoma metastatic to the thyroid gland in a 51-year-old gentleman with previous liposarcoma of the right thigh. Myxoid liposarcoma has a relatively good prognosis but tends to recur locally. Metastases affecting the thyroid gland are a rare entity and most commonly arise from the kidney, lung or breast. Clinical presentation, patterns of recurrence and prognosis of myxoid liposarcoma and metastases to the thyroid gland are discussed.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dacarbazine; Doxorubicin; Humans; Ifosfamide; Liposarcoma, Myxoid; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Thigh; Thyroid Neoplasms; Thyroidectomy; Tomography, X-Ray Computed

To evaluate the activity and toxicity of gemcitabine, ifosfamide and Navelbine (GIN) in advanced NSCLC.. Stage IIIB/IV NSCLC, WHO performance status <2 and bidimensionally measurable disease were required to enter the study. Gemcitabine 1000 mg/m(2) day 1 and 1000 or 800 mg/m(2) day 4, ifosfamide 3 g/m(2) day 1 (with mesna), Navelbine 25 mg/m(2) day 1 and 25-20 mg/m(2) day 4 were administered on an outpatient basis every 3 weeks for a maximum of six courses. Objective remissions (ORs) were evaluated every two courses. According to Simon's optimal two-stage design, more than 18 ORs out of 54 patients were required to establish the activity of this regimen.. The study group comprised 50 patients. Most patients had metastatic disease (79%) and nonsquamous histology (71%). The total number of courses administered was 200, with a median per patient of 4 (range 1-6). Myelosuppression, in particular leukopenia, was the most frequent toxicity: grade 3-4 neutropenia (WHO) occurred in 47% of the courses, while grade 3-4 thrombocytopenia and anemia affected, respectively, 6.6% and 3.5% of the courses only. Twelve episodes of febrile neutropenia were recorded, and three patients required hospital admission. No toxic deaths were reported. Nonhematological toxicity was generally mild and not clinically relevant. A total of 25 ORs (1 complete response and 24 partial responses) were obtained for a response rate of 52% (95% CI 37.4-66.5%). One-year survival was 46.5%.. The GIN combination showed promising activity against NSCLC with myelosuppression, in particular neutropenia, being dose limiting. This non-platinum-based triplet may be a valuable alternative to standard platinum-containing regimens and it is under evaluation in an ongoing randomized trial.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Drug Administration Schedule; Gemcitabine; Humans; Ifosfamide; Lung Neoplasms; Mesna; Middle Aged; Protective Agents; Vinblastine; Vinorelbine

Many investigators have reported the dose and schedule of VP-16 administration, but as yet they remain undetermined. VP-16 is one of the most active agents for several carcinomas and usually administered intravenously over 3 to 5 consecutive days in combination with other agents. Although, the development of new drugs recently reduces the use of VP-16 administration, VP-16 is still an important drug for the treatment of lung cancer and malignant lymphoma. In this paper, the combination therapy with VP-16, especially in the treatment of lung cancer and malignant lymphoma, are reviewed.

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Cisplatin; Clinical Trials, Phase II as Topic; Cytarabine; Etoposide; Humans; Ifosfamide; Lung Neoplasms; Lymphoma; Mesna; Methylprednisolone; Mitoxantrone

Topics: Adenocarcinoma, Clear Cell; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Papillary; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Lymphatic Metastasis; Mesna; Neoplasms, Second Primary; Radiotherapy, Adjuvant; Thyroid Neoplasms; Thyroidectomy; Uterine Neoplasms; Vincristine

Malignant triton tumor (MTT) is a relatively rare, aggressive tumor comprised of both malignant schwannoma cells and malignant rhabdomyoblasts. Because MTT frequently arises in the head and neck, the otolaryngologist must be aware of the nature of the tumor and its response to various treatment modalities.. This article reviews the treatment and outcome of all reported cases of MTT arising in the head and neck.. Although statistical analysis is limited by the short duration of follow-up of many patients, complete tumor resection appears to carry an improved chance of survival. Adjuvant radiation and chemotherapy may also improve survival, although a benefit of these therapies was not well demonstrated in this small series.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Child; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Etoposide; Fatal Outcome; Female; Head and Neck Neoplasms; Humans; Ifosfamide; Lung Neoplasms; Magnetic Resonance Imaging; Mesna; Neoplasm Recurrence, Local; Neurilemmoma; Radiotherapy Dosage; Vincristine

Ifosfamide is an analogue of cyclophosphamide that is active against a variety of solid tumors, including non-small cell lung cancer. In preclinical studies, ifosfamide had yielded an average response rate of 20% to 25% and a median length of survival of 4 to 5 months. With the introduction of mesna, hematologic toxicity is the major toxicity associated with ifosfamide use. Response is not affected by the schedule of drug administration, nor is the response rate compromised by oral delivery of ifosfamide. Neurotoxicity is greater with oral administration, however. Ifosfamide has been used in combination with many different agents, including cisplatin and etoposide and newer drugs like vinorelbine and paclitaxel. The results of the combination studies indicate improved response rates. However, results of randomized phase II trials suggest there may be no survival benefit with the addition of ifosfamide to establish drug combinations. Further study of ifosfamide in combination with newer drugs is appropriate.

Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase II as Topic; Expectorants; Humans; Ifosfamide; Liver; Lung Neoplasms; Mesna; Randomized Controlled Trials as Topic; Remission Induction; Survival Rate

Topics: Amputation, Surgical; Bone Neoplasms; Chemotherapy, Adjuvant; Child; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Humans; Ifosfamide; Leucovorin; Lung Neoplasms; Mesna; Osteosarcoma; Survival Analysis; Tennessee; Treatment Outcome; Vincristine

Pigmented banding of the nails and hyperpigmentation of hands and feet may occur during cyclophosphamide therapy. Ifosfamide, an analogue of cyclophosphamide, might be expected to cause similar pigmentary changes, but, to the knowledge of the authors, there are no reports of this.. The authors describe skin pigment changes in a 5-year-old patient receiving ifosfamide, MESNA, and etoposide for the treatment of relapsed Wilms tumor.. A review of the literature concerning cyclophosphamide-induced pigmentary changes is presented, along with a discussion of the possible correlation of renal dysfunction with pigmentary changes.. This case should alert health care providers to this uncommon adverse effect of ifosfamide.

Topics: Child, Preschool; Etoposide; Humans; Ifosfamide; Kidney Neoplasms; Lung Neoplasms; Male; Mesna; Pigmentation Disorders; Wilms Tumor

Observations have been made of the multiple-drug resistance phenomenon in mitomycin-exposed cells in vitro. Collateral resistance to anthracyclines and Vinca alkaloids was demonstrated in mitomycin carbon-treated 1-1210 cells in vitro. However, because it has also been found that this resistance can be reversed with agents such as verapamil and progestogens, it may be possible to effect a similar reversal in vivo. A study is currently being performed in patients with colorectal cancer, in which the potential for reversal is being tested. The pharmacokinetics of ifosfamide result in high cytotoxic specificity which, along with its therapeutic range, makes it a particularly active agent in the treatment of non-small cell lung cancer. Its urotoxicity is effectively controlled by the coadministration of mesna, a uroprotective agent.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Drug Resistance; Humans; Ifosfamide; Lung Neoplasms; Mercaptoethanol; Mesna; Mitomycins

We conducted a phase I trial of BNP7787 (disodium 2,2'-dithio-bis-ethane sulfonate, Tavocept™), a novel chemoprotective and antitumor enhancing agent administered in combination with paclitaxel and cisplatin. The primary aim was to determine a safe and potentially efficacious BNP7787 dose for preventing and mitigating paclitaxel- and cisplatin-induced toxicities and to evaluate for preliminary evidence of efficacy of treatment.. Twenty-two patients with stage IIIB/IV non-small cell lung cancer (NSCLC) received BNP7787 alone 1 week before co-administration of BNP7787 with paclitaxel followed by cisplatin. Twenty-one patients were treated with BNP7787 in escalating doses of 4.1-41.0 g/m² concurrently with paclitaxel 175 mg/m² and cisplatin 75 mg/m² every 3 weeks.. The appropriate dose was determined to be 18.4 g/m² of BNP7787 although no dose-limiting toxicity was observed up to 41.0 g/m². Mild intravenous site discomfort, thirst, and nausea were the most common toxicities. One patient developed grade 2 skin rash, which was severe enough to preclude further study treatment. The AUC(0-inf) of the metabolite mesna was approximately 6.3% of the AUC(0-inf) of BNP7787. Co-administration of paclitaxel and cisplatin did not appear to influence the pharmacokinetics of BNP7787 and mesna. The overall response rate was encouraging; 43% including 11 patients with prior chemotherapy.. The recommended dose for phase II/III studies is 18.4 mg/m² of BNP7787 in combination with paclitaxel and cisplatin. Further studies are warranted to assess whether BNP7787 prevents and mitigates common and serious paclitaxel- and cisplatin-related side effects and enhances the efficacy of paclitaxel and cisplatin in advanced NSCLC patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carcinoma, Non-Small-Cell Lung; Cisplatin; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasm Staging; Paclitaxel; Treatment Outcome

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

To investigate the prognostic value of systemic exposure to etoposide (Area Under the concentration Curve (AUC(VP16))) on overall survival (OS) in patients with small cell lung cancer (SCLC).. Data from 52 patients with limited stage (n=17) or metastatic (n=35) SCLC were analysed. They received at least two courses of etoposide (120mg/(m(2)day) on 3 days) combined with either doxorubicin-ifosfamide (AVI, n=29) or platinum compounds (carboplatin: n=16; cisplatin: n=7). Population pharmacokinetic-pharmacodynamic (PK-PD) study was performed using NON-linear Mixed Effect Model (NONMEM) and Splus software with univariate and multivariate analyses.. Etoposide plasma concentration vs. time was described by a two compartment model. Etoposide clearance (CL) was significantly dependant on serum creatinine (Scr). Ifosfamide (IFO) coadministration increased etoposide clearance by 28% (median CL(VP16): 2.42L/h vs. 1.89L/h, p<0.0005) leading to a reduced systemic exposure (median AUC(VP16): 260mgh/L vs. 339mgh/L). No influence of body surface area (BSA) on CL(VP16) was observed. Median percent decrease of absolute neutrophil count (ANC) after the first chemotherapy course was greater when etoposide 24h concentration was above 0.33mg/L (88% vs. 0%, p=0.028). Median OS was significantly longer in patients treated without ifosfamide (11.0 months vs. 7.0 months, p=0.049) and in patients with CL(VP16)<2.22L/h (14 months vs. 7 months, p=0.013) and AUC(VP16)>254.8mgh/L (11 months vs. 7 months, p=0.048). The independent prognostic factors regarding OS were LDH, CL(VP16) and AUC(VP16).. In this study it was found that CL(VP16) is reduced in patients with elevated serum creatinine, whilst ifosfamide coadministration increases CL(VP16) and reduces AUC(VP16), demonstrating the interaction between VP16 and ifosfamide. CL(VP16) and AUC(VP16) correlate significantly with overall survival of patients with SCLC patients receiving etoposide regimens.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carboplatin; Chromatography, High Pressure Liquid; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Kaplan-Meier Estimate; Lung Neoplasms; Male; Mesna; Metabolic Clearance Rate; Middle Aged; Prognosis; Proportional Hazards Models; Small Cell Lung Carcinoma

Small Cell Lung Cancer (SCLC) is increasingly being treated in the district general hospital setting. The search for an active regimen which can be given with the least toxicity and best outcomes led us to use a modified ICE (Ifosfamide, Carboplatin and Etoposide) regimen and modify it further by using oral mesna instead of intravenous mesna.. All patients selected to receive the modified ICE regime over a 5-year period were included in our study. All patients were assessed for performance status and prognostic factors. Only those with WHO performance status 0-1 and Manchester prognostic score 0-3 were considered for ICE chemotherapy. All patients were followed up for 1 year after recruitment was completed.. Median survival for all 32 patients was 18.4 months (CI 12.2-24.6) and for the 28 patients with limited disease the median survival was 19.9 months (CI 8.2-31.6). Toxicity levels were low with no neutropenic deaths. One patient died three days after treatment was started due to disease progression. A total of 6 patients remained alive one year after recruitment was completed. Five out of the 6 were followed up for at least 2 years.. Using this out-patient modified ICE regime we have achieved a median survival comparable to other active chemotherapy regimes for SCLC with no significant increase in toxicity.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Outpatients; Prognosis; Survival

Small-cell lung cancer (SCLC) is exquisitely chemosensitive, but few patients are cured by conventional chemoradiotherapy. Recent studies suggest that increased cytotoxic dose-intensity might improve survival. In this randomized phase II study, we tested the feasibility of dose intensification using sequential reinfusion of hematopoietic progenitors in whole blood.. SCLC patients with a favorable prognosis were treated with six cycles of ifosfamide, carboplatin, and etoposide (ICE), at 4-week (standard treatment) or 2-week (intensified treatment) intervals. Intensified treatment was supported by daily subcutaneous filgrastim injections and reinfusion of 750 mL of autologous blood collected immediately before each cycle.. Fifty consecutive patients were randomized to standard (n = 25) or intensified (n = 25) ICE. A total of 94% completed at least three treatment cycles, and 70% completed six cycles; 96% of treatments were given at full dose. The planned dose-intensity was 1.0 for standard and 2.0 for intensified ICE. The median received dose-intensity for cycles 1 through 3 was 0.99 (range, 0.33 to 1.02) for the standard treatment arm and 1.80 (range, 0.99 to 1.97) for the intensified treatment arm (P <.001). Over all six cycles, the median received dose-intensity was 0.95 (range, 0.17 to 1.03) for the standard treatment arm and 1.60 (range, 0.60 to 2.01) for the intensified treatment arm (P <.001). Febrile neutropenia was more common on the standard treatment arm (84% v 56%), resulting in more days of intravenous antibiotics (median, 10 v 3 days; P =.035). Transfusion requirements were similar in the two groups.. Sequential reinfusion of hematopoietic progenitors in whole blood can safely support substantial increases in dose-intensity of ICE chemotherapy for SCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Platelets; Carboplatin; Carcinoma, Small Cell; Combined Modality Therapy; Dose-Response Relationship, Drug; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Platelet Count; Quality of Life

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Drug Administration Schedule; Drug Costs; Etoposide; Female; Follow-Up Studies; Humans; Ifosfamide; India; Lung Neoplasms; Male; Mesna; Middle Aged; Patient Compliance; Poverty; Survival Analysis; Survival Rate; Treatment Outcome; Vincristine

A prospective randomized trial in small-cell lung cancer (SCLC) was performed to determine if intensification of the platinum dose by giving cisplatin and carboplatin in combination to patients with SCLC yields higher response rates and survival, than carboplatin alone in a combination chemotherapy regimen.. Between September 1992 and October 1997, 280 patients were included in a two armed prospective randomized trial, stratified by stage of disease, LDH and performance status. The treatment was in arm A: three courses induction chemotherapy with carboplatin (AUC = 4, day 1), cisplatin (35 mg/m2, days 2 and 3), teniposide (50 mg/m2, day 1-5), vincristine (1.3 mg/m2, day 1) every four weeks, followed by cyclophosphamide (3 g/m2, day 84), 4-epirubicin (4-epidoxorubicin) (150 mg/m2, day 112), and finally one course cisplatin, carboplatin, teniposide and vincristine, (days 140-144). Arm B also comprised a total of six courses, identical to those in arm A except for omission of cisplatin.. There were no significant differences in the overall treatment outcome for A vs. B, in terms of response rates (72% in both arms), complete response rates (40% and 34%, respectively), or median survival (314 days and 294 days, respectively). However, for patients with limited disease both the CR rate (54% vs. 37%, P < 0.05), overall survival (log-rank test, P < 0.05), and the two-year survival rate (11% vs. 6%, P < 0.05) were higher in the high-dose platinum arm compared to the carboplatin alone arm.. The intensification of platinum dose (cisplatin plus carboplatin) in combination chemotherapy significantly increased the complete response rate, overall survival and number of two-year survivors among SCLC patients with limited disease compared to combination therapy with carboplatin alone, suggesting that a more aggressive treatment to this category of patients is worthwhile, while no difference in treatment outcome was observed for patients with extensive disease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Cisplatin; Cyclophosphamide; Dose-Response Relationship, Drug; Epirubicin; Female; Humans; Infusions, Intravenous; Lung Neoplasms; Male; Mesna; Middle Aged; Prospective Studies; Survival Analysis; Teniposide; Treatment Outcome; Vincristine

The purpose of this study was to verify the kinetic response of the human marrow myeloid progenitor cells to the short term use of GM-CSF and its impact on the therapeutic activity of this three-drug cisplatinum containing regimen in non small cell lung cancer (NSCLC). Sixty patients with stage III-B and IV NSCLC were randomised to receive GM-CSF for 3 days, five days prior to the onset of chemotherapy. The chemotherapy regimen consisted of Mitomycin-C: 6 mg/m2 on day one, Ifosfamide: 2000 mg/m2 days 1 to 3, Mesna: 2000 mg/m2 days 1 to 3, Cisplatinum: 30 mg/m2 days 1 to 3, and was repeated every 4 weeks. All the patients received 30-50 Gy of radiotherapy to the primary and/or metastatic sites. There were positive correlations between stage of the disease, chemosensitivity of the tumor, number of chemotherapy cycles and overall survival (p=0.000). Administration of GM-CSF was an independent prognostic parameter in locally advanced and metastatic disease (p=0.041). In the GM-CSF receiving arm more courses could be given (117 versus 99, p=0.0415), and less courses were postponed (6 versus 22). In this arm, the mean of granulocyte nadir was higher (p=0.033) and mean time to granulocyte recovery became shorter (p=0.001) as the number of chemotherapy cycles increased. It was concluded that, dose intensification with GM-CSF prophylaxis is benefical in increasing the treatment tolerability by decreasing the intensity of granulocytopenia as well as providing rapid recovery.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Mitomycin; Recombinant Proteins; Survival Rate

The overall cure rate of locally advanced non-small cell lung carcinoma (NSCLC) remains poor. Although there have been encouraging reports of preoperative use of chemotherapy, more recent trend is the trimodal approach of radiation, chemo, and surgical-therapies. With the trimodal therapy, increased tumor response and resectability are reported, however, there are increased treatment related side effects. We observed that a relatively small dose of radiation given prior to induction chemotherapy greatly enhanced the tumor response to the chemotherapy without increased toxicity. A total of 18 patients (8 IIIA and 10 IIIB) were initially given 20 Gy of radiation therapy in 10 fractions and then received 2 courses of Taxol combination chemotherapy. The overall response rate was 83% (15/18) and 13 out of 18 patients underwent surgery. There was one postoperative death (not therapy related). It is speculated that the small dose of radiation therapy may have sensitized the tumor to subsequent chemotherapy, and we suggest a new hypothesis of "Radiation therapy induced chemotherapy sensitization".

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Humans; Ifosfamide; Lomustine; Lung Neoplasms; Mesna; Middle Aged; Neoplasm Staging; Paclitaxel; Survival Rate; Time Factors

Twenty-nine patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of cisplatin 20 mg/m2 days 1-3, ifosfamide 1500 mg/m2 days 1-2 (plus mesna as uroprotector) and vinorelbine 25 mg/m2 days 1 and 5; filgrastim was given at the dose of 300 microg subcutaneously from day 8 to day 15. A response rate of 28% was observed. The activity of this combination in an outpatient setting, with acceptable toxicity, has been demonstrated.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Disease Progression; Disease-Free Survival; Female; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Injections, Subcutaneous; Lung Neoplasms; Male; Mesna; Middle Aged; Protective Agents; Treatment Outcome; Vinblastine

To assess the toxicity and efficacy of high dose ifosfamide in stage IV NSCLC.. In a previous trial, we have determined maximum tolerated dose for 3-days ifosfamide treatment by 3-weeks schedule as 9 g/m2 according to hematologic tolerance. We therefore set up a phase II to study the toxicity and efficacy of this schedule in chemotherapy naive metastatic NSCLC. Ifosfamide (+ mesna 1 g/m2) was administered by a two hour infusion (3 g/m2) for three days every three weeks. Patients received three mesna bolus infusions (1 g/m2) at 4, 8 and 12 hours after the end of ifosfamide infusion. Antitumoral efficacy was performed after 2 cycles and treatment could be pursued for responding patients until disease progression. From september 1995 to January 1997, 31 patients have been included in this study. Median age was 60.7 years +/- 1.33 (41-70) for 27 males and 4 females. Patients (pts) presented metastases in lung for 10 pts, bone for 10 pts, liver for 6 pts, adrenal for 4 pts and multiorgan metastatic localisation for 1 patient. Seven patients were unassessable: 1 lost for follow-up, 1 sudden death, 5 treatment interruptions before evaluation time and 3 toxic deaths (9.6%).. neutropenia grade 4 (10 pts and 1 death), cardiotoxicity grade 4 (1 pt) and 2 deaths following neurotoxicity grade 4. We achieve 4 partial responses (13%, 95CI: 3.6-29.8), 10 progressive diseases (32.3%, 95CI: 16.7-51.4) and 10 stabilizations (32.3%, 95CI: 16.7-51.4). Median response duration was 91 days +/- 55 d. Median survival was 9.3 months, e.g. 280 days (8-863). Overall survival at one year is 48%.. This modality of high dose ifosfamide is as effective as standard monotherapy schedules in stage IV NSCLC. Unexpected toxicities particularly hematological ones could be due to a short duration of fractionated treatment. Results in term of survival leads us to further evaluate ifosfamide monotherapy treatment on a 5-day schedule basis.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Carcinoma, Non-Small-Cell Lung; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Survival Analysis; Treatment Outcome

Ifosfamide and paclitaxel are antineoplastic agents with broad activity and with different mechanisms of action. A Phase I trial was conducted to determine the maximum tolerated dose and associated toxicities of these agents when used in combination.. Patients with refractory, incurable solid tumors were entered on a 5-step Phase I trial of ifosfamide, given in doses of 2-3 g/m2 intravenous (i.v.) bolus for 3 days with mesna support, and paclitaxel, given in doses of 135-190 g/m2 i.v. by continuous infusion over 24 hours. Paclitaxel was given after the first dose of ifosfamide on Day 1.. Twenty-three patients were treated, and the maximum tolerated dose was the highest planned dose level of the trial: ifosfamide, 3 g/m2/day i.v. for 3 days, and paclitaxel, 190 mg/m2 i.v. over 24 hours. Hematologic toxicity was not dose-limiting, and although neutropenia occurred, it was brief (median, 2-4 days) and resulted in hospitalization for neutropenia and fever in only 7 of 111 courses of therapy. For patients treated at the highest dose level, only 1 of 50 courses of therapy resulted in hospitalization for neutropenia and fever. Nonhematologic toxicity also was not severe and no significant neuropathy occurred. Although patients entered into the study were heavily pretreated, responses were observed, particularly in patients with breast or ovarian carcinoma.. Ifosfamide and paclitaxel can be administered safely in the doses used in this study and there are indications of significant antitumor effect. Further studies are necessary to explore the antineoplastic activity of this regimen, particularly for patients with breast and ovarian carcinoma.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Colonic Neoplasms; Female; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasms; Neutropenia; Ovarian Neoplasms; Paclitaxel

To compare the pharmacokinetics of the approved I.V. (intravenous) mesna regimen and an investigational I.V.-oral regimen that could be used in outpatients who receive ifosfamide.. The I.V. regimen consisted of three I.V. mesna doses given at 0, 4, and 8 hours after ifosfamide administration. The investigational regimen included an I.V. mesna dose given concurrently with ifosfamide, followed 2 and 8 hours later by oral administration of mesna tablets. I.V. and oral mesna doses equaled 20% and 40%, respectively, of the ifosfamide dose. The study subjects were 12 lung cancer patients who received ifosfamide 1.2 g/m2 daily for 5 days. The patients were randomized to receive either the I.V.-oral or I.V. mesna regimen on day 1, followed by crossover to the other regimen on days 2 through 5 of ifosfamide treatment. The urinary profiles of mesna and dimesna excretion were determined on days 1, 2, and 5; pharmacokinetic parameters for blood samples were determined only on day 5.. During the first 12 hours after ifosfamide administration, the amount of mesna excreted and the profile of urinary mesna excretion was similar for both regimens; however, the I.V.-oral regimen showed less fluctuation in the excretion rate and higher trough values. During hours 12 to 24, about eightfold more mesna was excreted by patients given the I.V.-oral than the I.V. regimen.. These pharmacokinetic data show that the I.V.-oral regimen should be at least as uroprotective as the I.V. mesna regimen. Patients may also benefit from the I.V.-oral regimen because of the higher trough values during hours 0 through 12 and the sustained urinary mesna excretion during hours 12 through 24.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Agents, Alkylating; Cross-Over Studies; Humans; Ifosfamide; Infusions, Intravenous; Lung Neoplasms; Male; Mesna; Middle Aged

We have evaluated the combination of ifosfamide, carboplatin and etoposide (ICE regimen) along with mesna in 26 previously untreated patients with non small cell lung cancer (NSCLC). Thirteen stage III B and 13 stage IV patients received intermediate doses of ifosfamide (1000 mg/m2), carboplatin (120 mg/m2) and etoposide (120 mg/m2) given intravenously on day 1 to 3 every 4 weeks. Except for one patient who experienced grade 3 transient thrombocytopenia no major events of hematological or systemic toxicity were observed. Response rate (27%, 95% C.I., 10 to 44%), median duration of response (9 months, range 6-15), and survival (9.5 months, range 2-44+) were comparable to those achieved with conventional cisplatin-containing regimens. Our ICE combination, as compared to standard or high dose schedules appears effective, safe, well tolerated, and devoid of severe hematological toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Survival Analysis; Treatment Outcome

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

The oxazaphosphorine antineoplastic ifosfamide (IF) is metabolized by two different initial pathways: ring oxidation ("activation"), forming 4-OH-IF ("activated IF"), and side-chain oxidation with liberation of chloroacetaldehyde (CAA), forming the inactive metabolites 3-dechloroethylifosfamide or 2-dechloroethylifosfamide (3-DCE-IF, 2-DCE-IF). 4-OH-IF and 4-OH-IF-derived acrolein are thought to be responsible for IF-induced urotoxicity (hemorrhagic cystitis), whereas CAA may be involved in IF-associated nephrotoxicity (renal tubular damage). The thiol compound 2-mercaptoethane sulfonate sodium (mesna) has proved to inactivate sufficiently the urotoxic metabolites of oxazaphosphorine cytostatics and is therefore routinely given to patients receiving IF chemotherapy. The cumulative urinary excretion of IF, 4-OH-IF, 3-DCE-IF, 2-DCE-IF, mesna, and its disulfide dimesna was studied in 11 patients with bronchogenic carcinoma receiving IF on a 5-day divided-dose schedule (1.5 g/m2 daily) with concomitant application of mesna (0.3 g/m2 at 0,4, and 8 h after IF infusion). On day 1 the mean cumulative 24-h urinary recoveries (percentage of the IF dose) recorded for IF, 4-OH-IF, 3-DCE-IF, and 2-DCE-IF were 13.9%, 0.52%, 4.8%, and 1.5%, respectively. On day 5 the corresponding values were 12.2%, 0.74%, 9.9%, and 3.6%, respectively. This time-dependent increase in urinary excretion of IF metabolites, which is caused by rapid autoinduction of hepatic oxidative metabolism, may result in a higher probability for the development of urotoxic and nephrotoxic side effects during prolonged IF application. The mean 24-h urinary recoveries (percentage of the daily mesna dose) recorded for mesna/dimesna on day 1 (day 5) were 23.8%/45.2% (21.2%/39.8%), respectively. The mean molar excess of urinary reduced ("free") mesna over 4-OH-IF ranged from 11 to 72 on day 1 and from 6 to 40 on day 5. This indicates that although urinary excretion of 4-OH-IF rises with repeated IF application, mesna in standard doses should sufficiently inactivate the urotoxic IF metabolites.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biotransformation; Carcinoma, Bronchogenic; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cyclophosphamide; Drug Administration Schedule; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged

Thirty-five patients affected by stage III-IV non-small-cell lung carcinomas were treated with ifosfamide 3 gr/m2 plus MESNA as uroprotector on day 1 and vinorelbine 25 mg/m2 i.v. bolus on day 1 and 8. This cycle was repeated every 21 days. Over a total of 35 evaluable patients, the overall response rate was 34% (95% CL 18-54%). One patient experienced a complete response with a duration of 7.2+ months, and 11 patients a partial response with a mean duration of 5.9+ months. Seven patients had no change and 16 improved. The overall survival was 7.6+ months. Over a total of 145 cycles, the most frequent toxicity was myelosuppression, but grade 3 leukopenia and grade 2 thrombocytopenia were seen only in 14% and 9% of cases, respectively. Only one patient suffered grade 4 leukopenia. Gastrointestinal toxicity was minimal; only five patients (14%) complained of grade 3 vomiting. This combination regimen can be safely given on an outpatient regimen, but it is relatively active in advanced non-small-cell lung cancer. However, it should be noted that >50% of the patients in this series had a performance status of <80 and >50% were older than 65 years.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Humans; Ifosfamide; Lung Neoplasms; Mesna; Middle Aged; Vinblastine; Vinorelbine

Two studies were performed to determine the maximum tolerated dose (MTD) of paclitaxel and vinorelbine, respectively, in combination with a fixed dose of ifosfamide in previously untreated patients with stage IIIB or IV non-small cell lung cancer. Response rate and survival were also assessed. Both regimens were given with mesna and granulocyte colony-stimulating factor support. The maximum tolerated dose of paclitaxel in combination with 1.6 g/m2/d X 3 ifosfamide was 300 mg/m2, and the recommended dose for phase II study is 250 mg/m2. Among 31 patients treated with ifosfamide/paclitaxel, there were seven partial responses; additionally, 10 patients had either minor regression or stable disease. The maximum tolerated dose of vinorelbine in combination with 1.6 g/m2/d X 3 ifosfamide was 35 mg/m2/d X 3, and the recommended dose for phase II study is 30 mg/m2/d X 3. Among 42 patients treated with ifosfamide/vinorelbine, responses have been encouraging, and final analysis is pending. The dose-limiting toxicity for both regimens was neutropenia. These findings indicate that ifosfamide-containing combination chemotherapy regimens have activity in advanced non-small cell lung cancer and are well tolerated when administered with granulocyte colony-stimulating factor.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Tolerance; Expectorants; Female; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasm Staging; Neutropenia; Paclitaxel; Remission Induction; Survival Rate; Vinblastine; Vinorelbine

This Phase II study was designed to determine the efficacy of two chemotherapy regimens with G-CSF support for patients with advanced non-small cell lung cancer (NSCLC). One-hundred and one patients with Stage IIIB or IV NSCLC and performance status 0-1 were randomized to receive ifosfamide 2.0 g/m2 days 1-3, mesna 400 mg/m2 at 0, 4, 6 h days 1-3, cisplatin 33 mg/m2 days 1-3 or etoposide 200 mg/m2 days 1-3, cisplatin 35 mg/m2 days 1-3. Both groups received G-CSF 5 micrograms/kg SQ day 4 to the post day 11 absolute neutrophil count > 10 000. For the 47 eligible patients receiving ifosfamide/mesna/cisplatin, the response rate was 26% (95% confidence interval: 14-40%) and the median survival 7.5 months (95% confidence interval: 5.8-11.0 months). Grade 3 or worse toxicities were: neutropenia 75%, thrombocytopenia 70%, infection 21%. There were two treatment-related deaths due to infection. For course 1, the median absolute neutrophil count nadir was 1.3, platelet nadir 96 000 and incidence of febrile neutropenia 16%. For the 48 eligible patients receiving etoposide/cisplatin, the response rate was 21% (95% confidence interval: 11-35%) and median survival 5.8 months (95% confidence interval: 4.5-9.7 months). Grade 3 or worse toxicities were: neutropenia 90%, thrombocytopenia 58%, infection 29%. There were three treatment-related deaths due to infection. For course 1, the median absolute neutrophil count was 0.2, platelet nadir 80 000 and incidence of febrile neutropenia 33%. For both ifosfamide/mesna/cisplatin and etoposide/cisplatin, median duration of Grade IV neutropenia was short (< or = 4 days), time to subsequent courses 21 days and dose delivered > 95% of planned dose. Although G-CSF allowed full doses of drugs to be delivered on schedule, both ifosfamide/mesna/cisplatin and etoposide/cisplatin produced response rates and survival similar to other cisplatin-based regimens. In view of the significant cost of G-CSF and no obvious improvement in response rate, survival or toxicity profile, G-CSF cannot be recommended with these chemotherapy regimens for patients with advanced NSCLC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged

Chronic oral administration of anticancer drugs may offer therapeutic advantages.. A total of 68 patients with advanced non-small-cell lung cancer, not previously treated by chemotherapy, were randomized to receive either ifosfamide given orally (OSI) at a dose of 1 g/day for 14 days every 4 weeks, or as a 1-hour intravenous infusion (IVI) at a dose of 1.6 g/m2/day for 5 days every 4 weeks. According to the route of ifosfamide administration, patients received either mesna i.v. or mesna film-coated tablets for uroprotection.. Eight patients were found to be ineligible for the study and therefore excluded for all analyses. Thirty-three patients received IVI, and 27 patients OSI. One patient randomized to OSI died before treatment was initiated, leaving 59 patients fully evaluable for toxicity. Hematological toxicity was less severe for patients on OSI, but CNS toxicity was reported more frequently on OSI (39%; 12% grade III/IV), than on IVI (15%; 9% grade III/IV), which caused the premature close of the study. Other non-hematological adverse events were of modest clinical significance and comparable in both arms. Forty-nine patients were considered evaluable for response: in the IVI arm, 5 (17%) of the 29 evaluable patients obtained a partial remission, and 7 patients a no change (24%). In the OSI arm, 2 (10%) of the 20 evaluable patients obtained a partial remission, and 11 (52%) a stable disease.. Both arms have some activity in non-small-cell lung cancer; while OSI was less myelosuppressive than IVI, it was associated with a higher incidence of CNS toxicity. Oral administration of ifosfamide, in the schedule and daily dose tested here cannot be recommended.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Female; Humans; Ifosfamide; Infusions, Intravenous; Lung Neoplasms; Male; Mesna; Middle Aged

Alternating chemotherapy for small cell lung cancer has been tested in several studies. Some have shown positive results that have not been confirmed in other studies. In all of the studies, however, the degree of non-cross-resistance in the regimens was questionable. The EORTC Lung Cancer Study Group developed two equipotent regimens: (i) standard (CDE)-cyclophosphamide, doxorubicin, etoposide; (ii) (VIMP)-vincristine, carboplatin, ifosfamide, mesna, both non-cross-resistance. These two combinations were alternated and compared with the standard chemotherapy regimen in a group of 143 patients with extensive small cell lung cancer. Median survival was 7.6 months in the standard arm and 8.7 in the alternating arm (P = 0.243). Median time to progression was 5.8 and 6.4 months, respectively (P = 0.166). Median response duration was 7.0 and 6.8 months (P = 0.221). The use of two alternating regimens with a proven degree of non-cross-resistance did not result in any improvement in survival in patients with extensive small cell lung cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Blood Cells; Carboplatin; Carcinoma, Small Cell; Cyclophosphamide; Disease Progression; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Multivariate Analysis; Survival Analysis; Vincristine

We evaluated the efficacy and toxicity of the novel combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in patients with stage IIIB and IV non-small cell lung cancer (NSCLC). Between March 1993 and November 1994, 44 patients (17 stage IIIB; 27 stage IV) received a regimen consisting of IFX, 2 g/m2 in a 1-h infusion, days 1-3; mesna, 400 mg/m2 in an i.v. bolus at hours 0 and 4 and 800 mg orally at hour 8, days 1-3; and VNB, 35 mg/ m2 in a 20-min infusion, days 1 and 15. During the first course only, a half dose of VNB (17.5 mg/m2) was administered on days 8 and 22. Courses were repeated every 28 days. Forty patients were fully evaluable for response, and 44 were assessable for toxicity. Objective regression was recorded in 13 of 40 patients (33%). No patient achieved a complete response. Thirteen patients presented a partial response (33%); 17 (42%) had no change; and progressive disease was observed in 10 (25%). The median duration of response was 10 months, and the median time to treatment failure for the whole group was 4 months. Median survival was 11 months. The dose-limiting toxic effect was myelosuppression. Leukopenia occurred in 25 patients (57%) and was grade 3 or 4 in 8 patients (18%). Twelve patients (27%) developed peripheral neurotoxicity, while five had mild IFX-induced CNS toxicity. Phlebitis was observed in 15 of 30 patients (50%) who did not have central implantable venous systems. The IFX-VNB combination exhibited an activity against NSCLC that was among the highest reported for non-cisplatin-containing regimens, with a toxicity profile that was easily managed.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Brain; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Administration Schedule; Expectorants; Female; Humans; Ifosfamide; Leukopenia; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasm Staging; Peripheral Nerves; Phlebitis; Remission Induction; Survival Rate; Treatment Failure; Vinblastine; Vinorelbine

Recombinant human erythropoietin (r-Hu-EPO) is known to be effective in untreated cancer patients. Here we assess the possibility that r-Hu-EPO may also prevent or reduce anemia in patients who receive cytotoxic chemotherapy.. Thirty-six patients with small-cell lung carcinoma (SCLC) were enrolled onto a three-arm, randomized trial to investigate the effect of r-Hu-EPO on hemoglobin (Hb) levels and RBC and platelet (Plt) transfusions during chemotherapy. Bone marrow progenitors were studied before and after treatment. Two groups of patients received r-Hu-EPO at a dose of either 150 IU/kg (group 150) or 300 IU/kg (group 300) three times per week for the duration of chemotherapy. A control group did not receive r-Hu-EPO (group O). A maximum of six cycles of a chemotherapy regimen that consisted of vincristine, ifosfamide, carboplatin, and etoposide (VICE) were given to all patients. Hematologic parameters were measured weekly, and RBC or Plt transfusions were given for Hb levels less than 9 g/dL and Plt counts less than 20 x 10(9)/L.. Hb levels decreased in all patients, but onset of anemia was delayed in groups that received r-Hu-EPO (P = .002). A total of 116 U RBC were transfused in group 0, 54 in group 150, and 52 in group 300 (P = .017). In addition, there was a nonsignificant trend toward higher Plt counts and fewer Plt transfusions in patients who received r-Hu-EPO.. r-Hu-EPO at a dose of either 150 or 300 IU/kg three times weekly delays the onset of anemia and reduces RBC transfusion requirements in patients who undergo intensive chemotherapy for SCLC. A possible effect of r-Hu-EPO on platelet numbers deserves further study.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Colony-Forming Units Assay; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Etoposide; Female; Granulocytes; Hemoglobin A; Humans; Ifosfamide; Iron; Leukocyte Count; Lung Neoplasms; Macrophages; Male; Mesna; Middle Aged; Platelet Count; Platelet Transfusion; Recombinant Proteins; Vincristine

This study determined the maximum tolerated dose (MTD) of ifosfamide that could be given with high-dose cisplatin to non-small cell lung cancer (NSCLC) patients previously treated with non-platin-containing chemotherapy and to assess the efficacy of this combination. Twenty-three patients with inoperable NSCLC treated with one prior chemotherapy regimen received continuous infusion ifosfamide 1.2 g/m2 per day with MESNA for 5 days every 35 days and cisplatin 120 mg/m2. After one patient who received cisplatin as a single dose developed grade 4 nephrotoxicity and myelosuppression, cisplatin was given in four divided doses (30 mg/m2 per day) and the ifosfamide dose was lowered to 1.0 g/m2 per day, infused over 4 days. Dose-limiting grades 3 and 4 leukopenia was seen in 43%. A major objective response rate of 9% was observed. The 1-year survival was 30%, with a median survival of 6.4 months. The MTD of ifosfamide administered with cisplatin (30 mg/m2 per day for 4 consecutive days) to this population of patients is 1.0 g/m2 daily for 4 days. This combination produced limited anticancer activity and significant toxicity. Excessive toxicity was observed when cisplatin was given as a single dose with ifosfamide, and this schedule should not be used.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Remission Induction; Survival Analysis

This study was to define the efficacy of ifosfamide, mesna, carboplatin, and etoposide (ICE) in patients with metastatic non-small cell lung cancer (NSCLC). From September 1990 to October 1991, 33 patients were treated with ifosfamide/mesna 1.25 g/m2/day and etoposide 80 mg/m2/day intravenously from days 1 to 3, and carboplatin 300 mg/m2 on day 1 every 4 weeks. There were 20 male patients and 13 females. The median age was 65 (range: 38-79). Seventeen patients had a performance status (PS) of 0 or 1, and 16 had a PS of 2 or 3. All had measurable diseases. Nine had initial treatment for localized disease with concurrent radiation, 5-fluorouracil, and interferon-alpha 2b and four had radiation only. None had received chemotherapy for metastatic disease. There were nine partial responses (PR) (27.3%, 9/33) with a median response duration of 8 months (range: 2-16 months). Five patients had stable diseases (SD), which lasted for 3, 6+, 7+, 10+, or 13.4 months. The median survival was 8 months for PR and SD and 4 months for the entire group. Patients with PS of 2 or 3 were less likely to respond (18.8% vs 35.3%) and had a shorter median survival (2.7 months vs 6 months) than patients with better PS. Dose-limiting toxicity was myelosuppression. Seventeen (51.5%, 17/33) patients developed grade III-IV leukopenia with four septic episodes and three septic deaths. Grade III or IV thrombocytopenia was seen in five patients. Patients with prior radiation were significantly more prone to develop leukopenia (P < .005). Gastrointestinal toxicity was mostly mild. No neurologic or genitourinary toxicity was observed. In conclusion, ICE is active in patients with advanced NSCLC and good PS. Besides myelosuppression, it is well tolerated. Further study is indicated to evaluate if granulocyte-colony stimulating factor can reduce myelosuppression from ICE in good PS patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Remission Induction; Survival Analysis

This report describes the unusually high response rate of metastatic synovial sarcoma to high dose ifosfamide (14-18 g/m2) when that drug was used to treat 13 consecutive patients with recurrent metastatic synovial sarcoma before surgery (or thoracotomies) to provide optimal salvage therapy for these patients.. Thirteen patients with recurrent or pulmonary metastatic synovial sarcoma seen at the Cedars-Sinai Comprehensive Cancer Center (Los Angeles, CA) from April, 1989 through January, 1993 were treated with high dose ifosfamide (14-18 g/m2). Ifosfamide was infused at the dose of 2 g/m2 over a 4-hour bolus infusion, followed by 2-g/m2 24-hour continuous infusions of ifosfamide, for a total of 14 or 18 g/m2 (6-8 days). Mesna (Mesnex, Bristol-Myers Oncology, Princeton, NJ) was infused with the ifosfamide at equimolar doses. Supplemental sodium bicarbonate (180 mEq) was given daily to prevent severe acidosis. Nine of the thirteen patients were treated with prior chemotherapy for their primary tumors. Prior chemotherapy consisted of doxorubicin (Adriamycin, Adria Labs, Dublin, OH) in all patients and doxorubicin combined with cisplatin in eight of them.. All 13 patients had objective responses to high dose ifosfamide chemotherapy. There were nine partial responses and four complete responses. Five of the patients died of disease at 20-40 months (median, 27 months) from initial therapy. Eight patients have survived from 2 to 43 months (median, 20 months) from initial therapy, and three of these patients are disease free. Those patients surviving disease free had successful surgical removal of their residual metastatic disease after chemotherapy.. Metastatic synovial sarcoma appears to be particularly sensitive to high dose ifosfamide chemotherapy. This experience suggests that there is a role for high dose ifosfamide chemotherapy in preoperative and postoperative adjuvant chemotherapy for primary synovial sarcoma, which is usually always a high grade malignant lesion with a poor prognosis after surgery alone.

Topics: Adolescent; Adult; Female; Humans; Ifosfamide; Infusions, Parenteral; Lung Neoplasms; Male; Mesna; Neoplasm Recurrence, Local; Sarcoma, Synovial

The purpose of this trial is to assess the possible benefit of neoadjuvant chemotherapy before surgery in patients with operable non-small cell lung cancer. Patients with operable stages I (except T 1N0), II, or IIIA disease are eligible for this ongoing trial. Patients are randomized into two arms. Surgery is performed first in group I; patients found to have T3 tumors or N2 lymph nodes are given postoperative radiotherapy. Group 2 patients start with two cycles of chemotherapy; following surgery, two more cycles are administered in responder patients and, as in group I, patients with T3 tumors or N2 lymph nodes are given radiotherapy. Chemotherapy is the MIP protocol: mitomycin 6 mg/m2 day I, ifosfamide 1.5 g/m2 days 1 to 3, cisplatin 30 mg/m2 days I to 3, and mesna 1,200 mg/m2 days 1 to 3. One hundred fifty patients were enrolled between June 1991 and September 1993. By the time this report was prepared, 117 patients had completed all assigned treatment, 63 in group I and 54 in group 2. There were two ineligible patients, one in each group. Forty-nine patients underwent thoracotomy in the chemotherapy-surgery group and 62 in the surgery-only group. There was only one progression after two cycles of chemotherapy. Rates of exploratory and incomplete surgery were 17% in group I and 12% in group 2. The trial is ongoing.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Mitomycin; Mitomycins; Survival Analysis

Topics: Amputation, Surgical; Bone Neoplasms; Chemotherapy, Adjuvant; Child; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Humans; Ifosfamide; Leucovorin; Lung Neoplasms; Mesna; Osteosarcoma; Survival Analysis; Tennessee; Treatment Outcome; Vincristine

The Goldie-Coldman hypothesis of alternating non-cross resistant combination chemotherapy regimens for small-cell lung cancer has never been adequately evaluated. In previously reported studies non-cross resistance and/or equipotency of the combinations used had not been tested before the phase III study was started. We describe two combination chemotherapy regimens with comparable efficacy against small-cell lung cancer and present a phase II test of their possible non-cross resistance. Patients clinically resistant to cyclophosphamide, doxorubicin and etoposide (CDE), were treated with the second-line regimen consisting of vincristine, ifosfamide, mesna and carboplatin (VIMP) (n = 25). This resulted in 1 complete and 14 partial responses, response rate 60% [95% confidence interval (CI): 38.7-78.9%]. Patients clinically resistant to vincristine, carboplatin (n = 22) or ifosfamide, mesna, carboplatin (n = 21) were treated with CDE, resulting in 6 complete responses and 16 partial responses, response rate 51% (95% CI: 35.5-66.7%). The clinical value of such a degree of non-cross resistance has to be evaluated in a phase III study.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Cyclophosphamide; Doxorubicin; Drug Resistance; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Prognosis; Vincristine

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

This Phase I study was designed to determine the maximum tolerated dose of ifosfamide-mesna with a fixed dose of cisplatin without growth factor or hematopoietic precursor support.. Twenty-five patients with previously untreated advanced non-small cell lung cancer were treated at four dose levels. Initially, the cisplatin dose was 100 mg/m2 given on day 1. Seven patients were treated with ifosfamide 2.0 g/m2 days 1 to 3, and six patients received ifosfamide 2.5 g/m2 days 1 to 3. Mesna was given at 20% of the ifosfamide dose at 0, 4, and 6 hours after ifosfamide. Cycles were repeated every 4 weeks.. Dose-limiting toxicities (myelosuppression and renal toxicity) were seen at dose level 2 (ifosfamide 2.5 g/m2). Because 5 of the first 13 patients experienced Grade 3 renal toxicity, the study was amended to give cisplatin in divided doses. An additional six patients each were treated at dose level 3 (ifosfamide 2.0 g/m2 days 1-3) and dose level 4 (ifosfamide 2.5 g/m2 days 1-3) with cisplatin 33 mg/m2 days 1 to 3. Dose-limiting toxicity (myelosuppression) was reached at ifosfamide 2.5 g/m2. No further Grade 3 renal toxicity was seen. Grade 3 or worse toxicities were seen as follows: neutropenia 80%, thrombocytopenia 48%, nausea/vomiting 36%, anemia 32%, renal 20%, central nervous system 16%, and infection 16%. Two toxic deaths occurred, both with infection, renal failure, and neutropenia. Partial responses were seen in 8 of 25 eligible patients (32%).. The maximum tolerated dose in this group of patients was defined as ifosfamide 2.0 g/m2 days 1 to 3 when given with cisplatin 33 mg/m2 days 1 to 3. When combining high-dose cisplatin with ifosfamide, it is advisable to give cisplatin in divided doses.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Female; Fluid Therapy; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Neutropenia; Thrombocytopenia; Vomiting

In this report, the results of two phase II studies and one pilot study of second-line carboplatin-based chemotherapy for small cell lung cancer are described. Carboplatin plus vincristine given with or without ifosfamide resulted in response rates of 36% and 53%, respectively, in so-called chemotherapy-resistant patients. Toxicity of the carboplatin/vincristine regimen was mild (hematologic toxicity grade 4 was seen with 13% of the courses), whereas the combination including ifosfamide resulted in grade 4 thrombocytopenia in 57% of the courses and grade 4 leukocytopenia in 49%. A partial response was seen in one of nine patients with progression of brain metastases after chemotherapy, and in three patients the neurologic function score improved, with minor tumor reduction evident on computed tomography scan of the brain. We conclude that carboplatin is a useful agent for second-line chemotherapy in patients with an early relapse after induction chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carboplatin; Carcinoma, Small Cell; Clinical Trials, Phase II as Topic; Cyclophosphamide; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Pilot Projects; Remission Induction; Survival Rate; Vincristine

In order to evaluate the preventive efficacy, safety and usefulness of mesna (Sodium 2-mercaptoethane sulfonate) against ifosfamide-induced urinary disorders, a placebo-controlled double-blind comparative study was performed. Ifosfamide was administered by intravenous drip infusion at a daily dose of 2 g/m2 for 5 consecutive days, and mesna was intravenously administered at 20% of the ifosfamide dose, three times daily for 5 consecutive days. The results obtained are as follows. (a) Of 101 accrued patients, 91 patients were evaluated consisting of 45 for the mesna group and 46 for the placebo group. There was no intergroup difference in the number of the evaluated cases and patient characteristics. (b) Micturition pain and feeling of residual urine graded as moderate or severe were not observed for the mesna group, but were observed for the placebo group with incidences of 19.6% (9/46) for micturition pain and 15.2% (7/46) for feeling of residual urine; the intergroup differences in the appearance of these urinary symptoms were statistically significant (P = 0.0003 for micturition pain; P = 0.0009 for feeling of residual urine). The incidence of hematuria graded as moderate or severe was 6.7% (3/45) in the mesna group, which was significantly lower than the 32.6% (15/46) in the placebo group (P = 0.0008). (c) No side-effect attributable to mesna was observed. (d) A judgment of "useful" was obtained in 80.0% (36/45) of the patients treated with mesna, which was significantly higher than the 34.8% (16/46) of the patients treated with placebo (P = near 0). On the basis of the above results, we conclude that the preventive efficacy, safety and usefulness of mesna against ifosfamide-induced urinary disorders have been well demonstrated in this study.

Topics: Adult; Aged; Double-Blind Method; Female; Hematuria; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Pain; Urination Disorders; Urologic Diseases

Two studies were carried out (A and B) in order to assess the effectiveness of ifosfamide administered with mesna (IFO/M) in the treatment of small cell lung cancer. The first study (A) was a cross-over study; the second (B) was a randomized trial, and in B IFO/M was evaluated earlier in the course of the disease. IFO/M given be infusion is effective as second-line therapy and can be administered with other cytotoxics at the doses reported here earlier in the course of the disease. The complete remission rates were high.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Drug Evaluation; Humans; Ifosfamide; Infusions, Intravenous; Lung Neoplasms; Mercaptoethanol; Mesna

High-dose ifosfamide (one or two courses of 6 g/m2) with or without mesna was administered to 13 patients with advanced non-small cell lung cancer. The protective effect of 2-mercapto-ethane sulfonate (mesna) against the urotoxic side effects induced by ifosfamide was examined by a randomized crossover trial. A significant reduction in the incidence of hematuria was observed in the patients receiving mesna. Macroscopic hematuria was observed in only one patient who received treatment with mesna versus seven patients treated with ifosfamide alone. Other symptoms, such as frequency and dysuria, tended to be diminished in the patients receiving mesna, although the difference was not statistically significant. Our results suggest that mesna is effective in preventing or diminishing ifosfamide-induced hemorrhagic cystitis. Concomitant use of mesna should allow the administration of a high dose of ifosfamide although more extensive studies are needed to define the optimal dose and schedule of administration of mesna to prevent or attenuate the hemorrhagic cystitis.

Topics: Adult; Aged; Clinical Trials as Topic; Cystitis; Female; Hemorrhage; Humans; Ifosfamide; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Middle Aged; Random Allocation

Eighteen patients with untreated small-cell cancer of the lung have been treated with cyclophosphamide 200 mg/kg on two occasions at an interval of four weeks. An additional eight patients received etoposide in addition to cyclophosphamide. Measurements of tumor volume were made by thoracic computed tomographic (CT) scan before and after each cycle. When compared with our previous study in which only one cycle of cyclophosphamide was given, the double procedure did not increase response rate, decrease the incidence of local relapse, or prolong the relapse-free interval. Survival after relapse was shorter with two cycles of chemotherapy mainly due to greater difficulty in administering further chemotherapy. The CT scans showed a decrease in tumor volume from 99.2 cc to 21 cc after the first cycle, but a smaller decrease to 14.1 cc after the second. These results show that the rapid emergence of drug resistance imposes limitations on the use of very high-dose cytotoxic chemotherapy.

Topics: Adult; Aged; Bone Marrow Transplantation; Carcinoma, Small Cell; Clinical Trials as Topic; Cyclophosphamide; Female; Humans; Lung Neoplasms; Male; Mesna; Middle Aged; Time Factors; Tomography, X-Ray Computed

Thirty six patients with advanced solid tumors (24 lung: 3 oat-cell, 14 squamous, 7 adenocarcinomas, 3 soft tissue sarcomas, 6 breast carcinomas; 1 seminoma; 2 ovarian adenocarcinomas) entered a phase II study of high-dose ifosfamide (IF) administered in combination with the uroprotective agent sodium 2-mercapto-ethane-sulfonate (Mesna). Fourteen patients had prior treatment; most patients with lung cancer (22/24) were previously untreated; all had measurable disease. The patients median age was 59 (range 31-74). IF was given at 1.8 g/m2 days 1-5 q 4 weeks. Mesna was given after each IF injection at 0, 4 and 8 h randomly, either i.v. (0.36 g/m2) or orally (0.72 g/m2). Twenty-four patients had greater than or equal to 3 courses of therapy, 9 had 2 courses, and 3 had only 1 course; 129 courses were evaluated for toxicity. Mesna was given orally (17 patients, 57 courses) or i.v. (19 patients, 72 courses). The following side-effect were observed: no gross hematuria, microhematuria (14 courses), transitory mild proteinuria (34 courses), leukopenia grade I-II ECOG (26 courses), anemia grade I ECOG (31 courses), 1 case of pancytopenia, alopecia (31 patients), nausea (moderate, 33 courses; severe, 6 courses), vomiting (moderate, 17 courses; severe, 1 course). Five patients showed a partial response (1 oat-cell carcinoma, 2 with squamous lung cancer, 1 with ovarian carcinoma, 1 with breast carcinoma), 14 showed a minor response (2 patients with oat-cell carcinoma, 2 with lung adenocarcinoma, 5 with squamous lung cancer, 1 with seminoma, 1 with sarcoma, 1 with ovarian carcinoma), and 14 showed progression of disease (7 patients with squamous cell lung cancer, 4 with lung adenocarcinoma, 1 with sarcoma, 2 with breast carcinoma). Considering partial plus minor responses, ifosfamide produced some degree of tumor reduction (PR + MR) in 12/23 (52.1%) lung cancer patients. The data reported support the conclusions that Mesna can prevent high-dose IF bladder toxicity, that IF is active in advanced solid tumors, including lung cancer, and that the IF + Mesna combination is a generally safe treatment procedure.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasms; Urinary Bladder

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

In 8 patients receiving intravenous isophosphamide 2 g/m2 at 2-week intervals for advanced bronchogenic carcinoma the protective effect of 2-mercaptoethane sulphonate sodium (mesnum) against isophosphamide-induced urothelial toxicity was tested in a single-blind crossover trial. With isophosphamide alone, 7 of the 8 patients developed either haematuria or symptoms of bladder irritation; when mesnum was given in addition, only 1 patient had microhaematuria and frequency, and this was in association with a urinary-tract infection. 5 patients then received fifteen courses of isophosphamide in increasing doses of 4 to 8 g/m2 i.v. with mesnum. In contrast to previous experience with isophosphamide at this high dosage, frank haematuria was never seen, microhaematuria was seen after only three courses, and mild dysuria after only one course. Pharmacokinetic studies showed that mesnum did not interfere with the metabolism of isophosphoramide or its active anti-tumour metabolite, isophosphoramide mustard. Mesnum therefore enhances the therapeutic ratio of isophosphamide and may thereby increase its clinical efficacy.

Topics: Acrolein; Carcinoma, Bronchogenic; Clinical Trials as Topic; Cyclophosphamide; Female; Hematuria; Humans; Ifosfamide; Kinetics; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Phosphoramide Mustards; Urinary Bladder

We reported the efficacy and safety results of high-dose, continuous-infusion Ifosfamide,in patients with advanced thymoma (TM) and thymic carcinoma (TC).. This was a multicentric, prospective study in patients with advanced TM or TC, who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis or anti-PD(L)1 was allowed. Patients received Ifosfamide (1 g/m2/day) and sodium-2-mercaptoethanesulfonate (1 g/m2/day), as continuous infusion, via a portable pumps for 14 consecutive days. Treatment was administered every 4 weeks until progression or unacceptable toxicity, up to a maximum of 6 cycles. The primary endpoint was the overall response rate (ORR) assessed by RECIST1.1. Secondary endpoints included disease control rate (DCR), Progression-free survival (PFS), overall survival (OS), and safety.. Eighteen patients were enrolled from October 2020 to January 2022. Twelve patients had a TC, 5 a TM and 1 a mixed TM/TC. Sixty-one percent of patients (11/18) had stage IVB disease according to Masaoka-Koga, and 39% (7/18) had an ECOG-PS 2. The median number of previous lines of therapy was 2 (range:1-5), and 72% (13/18) and 61% (11/18) of patients were pretreated with an anti-angiogenesis drug and an anti-PD(L)1 drug respectively. The ORR and the disease control rate (DCR) were 28 % (95 %CI: 10 %-53 %) and 67 % (95 %CI: 41 %-86 %), respectively. The median follow-up for PFS was 17.3 months (95 %CI: 4.3-NA), and median PFS was 5.4 months (95 %CI: 2.9-6.4). The median duration of response and SD was respectively 19.6 months (95 %CI: 3.5-NA) and 6.0 months (95 % CI: 3.8-6.4). In patients with TC, the ORR and DCR were 15 % (95 % CI: 2 %-45 %) and 54 % (95 % CI: 25 %-81 %), respectively. In the subgroup of 5 patients with TM, 2 PR and 3 SD were observed. Most patients had only mild (grade 1-2) AEs, the most common being nausea and vomiting (39%; 7/18) and transaminases elevation (33%; 6/18). Twenty-two percent of patients (4/18) experienced an AEs of grade 3 and required ifosfamide dose reduction. No patients had severe AEs.. High-dose continuous-infusion Ifosfamide can be considered as a valuable treatment option in patients with advanced thymic epithelial tumors.

Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Ifosfamide; Lung Neoplasms; Mesna; Progression-Free Survival; Prospective Studies

The role of chemotherapy in the treatment of myxofibrosarcoma is unclear. There are no randomized clinical trials evaluating the therapeutic effect of chemotherapy on myxofibrosarcoma. We report, to the best of our knowledge, the first case of myxofibrosarcoma successfully treated with mesna, pirarubicin, ifosfamide and dacarbazine (modified MAID) regimen. The patient achieved complete remission evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST).

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Fibrosarcoma; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna

Ameloblastoma is generally characterized as a benign tumor originating in odontogenic epithelium. However, few cases of metastatic malignant ameloblastoma have also been reported. Due to the low incidence of malignant ameloblastoma, there is no established treatment regimen. To explore effective treatment for malignant ameloblastoma, we reported this case study.. This report described a case of a 28-year-old malignant ameloblastoma female patient with multiple metastasis (brain and lung).. The patient presented ameloblastoma of the left mandible in 2012. Three years later, local recurrence and brain metastasis was observed during a follow-up examination. Five years later, malignant ameloblastoma was detected by imaging and immunohistochemistry in the bilateral multiple pulmonary nodules and mediastinal lymph nodes.. The patient was initially treated with tumor resection. Three years later after local recurrence and brain metastasis, she was accepted the extensive mandibulectomy supplemented with brain stereotactic body radiotherapy (SBRT). When diagnosed with pulmonary metastasis, the patient received combined chemotherapy regimen of MAID (mesna, adriamycin, ifosfamide and dacarbazine) for 6 cycles.. The efficacy evaluation was partial remission (PR) after the 6 cycles of MAID. The last patient follow-up was July 24th 2018, and no evidence of progression was observed. The progression-free survival (PFS) of the patient was more than 9 months.. Surgical resection is the optimal treatment for locally recurrent ameloblastoma. SBRT may be an effective treatment for unresectable oligometastasis of malignant ameloblastoma. Finally, combined chemotherapy of MAID showed encouraging effects in the management of metastatic malignant ameloblastoma.

Topics: Adult; Ameloblastoma; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Dacarbazine; Disease-Free Survival; Doxorubicin; Female; Humans; Ifosfamide; Jaw Neoplasms; Lung Neoplasms; Mesna; Neoplasm Metastasis; Neoplasm Recurrence, Local; Treatment Outcome

Pulmonary pleomorphic carcinoma (PC) is a rare type of lung tumor with a dismal prognosis. There is no consensus on a chemotherapy regimen for PC, and conventional platinum-based chemotherapy has been associated with disappointing response rates and PFS. In searches for a new regimen, the sarcomatoid (spindle or giant cell) component has been assumed to be susceptible to chemotherapy used for soft tissue sarcoma.. The medical records of 17 patients who received mesna, doxorubicin, ifosfamide, and dacarbazine (MAID) for advanced PC between January 2010 and February 2017 were retrospectively analyzed for clinicopathological features and outcomes.. The median age was 59 years. Sixteen patients were male, and only one patient had never smoked. Six patients achieved partial response to MAID, leading to an objective response rate of 35%. The median PFS was 2.8 months, and the median OS was 8.7 months. Hematologic toxicity-related adverse events were the most frequent, which comprised grade 3-4 anemia in 35% of patients, neutropenia in 47%, thrombocytopenia in 24%, and febrile neutropenia in 29%. No febrile neutropenia was reported in patients who received 5-day granulocyte-colony stimulating factor (G-CSF) prophylaxis. Most adverse events resolved without complications, except for one death due to sepsis. MAID is an effective, and possibly important, regimen for PC. MAID could be more safely used in clinical practice with appropriate dose modifications and G-CSF primary prophylaxis according to patients' status.

Topics: Adult; Aged; Dacarbazine; Doxorubicin; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasms, Complex and Mixed; Retrospective Studies; Sarcoma; Survival Analysis

To analyze the clinical features, treatment and prognosis of Stage IV alveolar soft part sarcoma.. To analyze the clinical and pathological features, therapeutic methods and follow-up results in 21 patients with stage IV alveolar soft part sarcoma. There were 11 males and 10 females, in the age of 26-57 years (average 37.0 years old). All the 21 patients had metastasis: nine cases had multiple pulmonary metastasis, three cases had multiple pulmonary and brain metastasis, two cases had multiple brain metastasis, two cases had multiple pulmonary and bone metastasis, two cases had single pulmonary metastasis, one case had single bone metastasis, one case had single brain metastasis and one case had single soft tissue metastasis. Eight patients were treated by surgical operation, including five cases of complete resection for the primary and (or) metastatic tumor and 3 cases of palliative operation for the primary tumor. All patients received chemotherapy, including seven cases of CAVD regimen and 14 cases of MAID regimen treatment. One patient with single bone metastasis and five patients with multiple brain metastasis received post-operative whole brain radiation therapy.. All the eight patients with surgical operation had healing by first intention, and pathological examination showed that seven patients achieved R0 surgical margin and one case with R2 status. One patient with single brain metastasis had recurrence after operation. The toxic and adverse reactions of all patients treated with chemotherapy were tolerable. Among them, 17 cases had stable disease and 4 cases had disease progression after chemotherapy. The disease control rate (DCR) was 81.0%. The DCR of patients with CAVD regimen chemotherapy was 85.7% and that of patients treated with MAID regimen was 78.6% (P = 0.862). All patients were followed up for 8 - 86 months (average 32.4 months). The median survival time of all patients was 32.6 months. The 2-year survival rate was 55.1% and the 5-year survival rate was 21.8%. The median survival time in the patients with complete resection was 60.0 months, and that in patients with palliative operation was 27.0, showing a significant difference between them (P = 0.048). The median progression-free survival in patients with complete excision was 57.2 months and that in patients with palliative operation or without operation was 19.6 months, with a significant difference (P = 0.029). The median survival time in patients who received CAVD regimen chemotherapy was 30.0 months, and that in patients with MAID regimen was 51.0 months, with a non-significant difference (P = 0.511). The median progression-free time in patients with CAVD regimen chemotherapy was 13.0 months, and that in patients with MAID regimen was 38.0 months, also with a non-significant difference (P = 0.066).. Alveolar soft part sarcomas are rarely seen and highly malignant tumors, and the prognosis of stage IV ASPS is poor. Complete resection of all tumors is the key of successful treatment of Stage IV ASPS, and the site and number of tumor metastasis are important factors affecting prognosis. The curative effects of radiotherapy and chemotherapy for ASPS need to be further investigated.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Dacarbazine; Disease-Free Survival; Doxorubicin; Female; Follow-Up Studies; Humans; Ifosfamide; Lower Extremity; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Particle Accelerators; Remission Induction; Salvage Therapy; Sarcoma, Alveolar Soft Part; Soft Tissue Neoplasms; Survival Rate

When oncologists encounter patients with pulmonary pleomorphic carcinoma, most cases have recurrent disease after surgery or metastatic disease. Previous studies have suggested that patients with pleomorphic carcinoma have extremely poor responses to chemotherapy regimens commonly used for non-small cell lung cancer and have a dismal prognosis. This report describes two consecutive patients with platinum-refractory pulmonary pleomorphic carcinoma who received doxorubicin, ifosfamide plus dacarbazine chemotherapy. Both patients showed dramatic responses to this combination chemotherapy and the treatment effect was sustained for 7 and 9 months, respectively. Our report strongly suggests that the treatment approaches to patients with pulmonary pleomorphic carcinoma should differ from the approaches to patients with other common types of non-small cell lung cancer. Doxorubicin, ifosfamide plus dacarbazine chemotherapy may have an important role in the treatment of patients with pulmonary pleomorphic carcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Dacarbazine; Doxorubicin; Drug Resistance, Neoplasm; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Organoplatinum Compounds; Salvage Therapy; Survival Rate; Treatment Outcome

Topics: Adult; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bowman Capsule; Dacarbazine; Deoxycytidine; Disease Progression; Docetaxel; Doxorubicin; Endothelium, Vascular; Fibrosarcoma; Gemcitabine; Glomerulonephritis, Membranoproliferative; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Muscle Neoplasms; Podocytes; Proteinuria; Taxoids; Vascular Endothelial Growth Factor A

Malignant fibrous histiocytoma (MFH) of the kidney is a rare sarcoma that often undergoes local recurrence and/or distant metastasis. However, little is known about the outcome of metastatic diseases. We present the case of a 46-year-old male suffering from renal MFH with pulmonary metastasis, who has undergone complete response for 3 years after surgical resection and MAID chemotherapy. He is now well, and without any evidence of recurrent disease.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Chemotherapy, Adjuvant; Dacarbazine; Doxorubicin; Histiocytoma, Malignant Fibrous; Humans; Ifosfamide; Kidney Neoplasms; Lung Neoplasms; Male; Mesna; Middle Aged; Nephrectomy; Thoracoscopy; Tomography, X-Ray Computed; Treatment Outcome

The role of tandem high-dose chemotherapy (HDC) with autologous peripheral hematopoietic progenitor cell rescue (APHPCR) in patients with Ewing Family Tumors (EFT) is controversial. We initiated treatment for eight consecutive patients with high-risk EFT with HDC and APHPCR from 1992 to 2003. There were no treatment related deaths. Four patients remain in complete remission, including three who did not undergo local therapy to bone at either the primary or metastatic sites. Our experience has shown that treatment of EFT patients with tandem HDC with APHPCR may benefit a subgroup of high-risk patients in whom optimal local therapy is not possible.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; Feasibility Studies; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Neoadjuvant Therapy; Neuroectodermal Tumors, Primitive; Pelvic Bones; Peripheral Blood Stem Cell Transplantation; Remission Induction; Risk; Sarcoma, Ewing; Scapula; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Vincristine

The response of adult soft tissue sarcoma (STS) to chemotherapy is uncertain. This study was to evaluate the role of chemotherapy in treating adult soft tissue sarcoma.. Clinical data of 109 adult soft tissue sarcoma patients, treated with chemotherapy at Cancer Center of Sun Yat-sen University from Jan. 2000 to Dec. 2005, were analyzed.. Of the 109 patients, 66 received palliative chemotherapy, 40 received adjuvant chemotherapy, and 3 received neoadjuvant chemotherapy. The overall response rate for first line chemotherapy was 22.7%. The median survival was 16.9 months. The 1-and 2-year survival rates were 63.6% and 33.3%. The patients with lung metastasis had a significantly longer median survival than those with liver metastasis did (25.1 months vs. 11.8 months, P<0.05). MAID and CYVADIC were the most commonly used first-line chemotherapy regimens; the response rates were 28.0% and 22.2%, respectively. When anthracycline and/or standard dose ifosfamide failed, the patients could still benefit from high dose ifosfamide (14.0 g/m(2)). The median survival was significantly shorter in the patients who got metastasis within 6 months after diagnosis than in those that got metastasis more than 6 months after diagnosis (11.8 months vs. 42.9 months, P=0.04). Of the 40 patients who received adjuvant chemotherapy, 16 developed progression during follow-up: 10 had relapse and 6 had distant metastasis.. MAID and CYVADIC are two effective chemotherapy regimens for adult soft tissue sarcoma. We recommend to take a high dose ifosfamide when anthracycline and/or standard dose ifosfamide failed. The patients with liver metastasis are more resistant to chemotherapy than those with lung metastasis. Developing metastasis within 6 months after diagnosis is a poor prognostic factor.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cyclophosphamide; Dacarbazine; Doxorubicin; Extremities; Female; Follow-Up Studies; Humans; Ifosfamide; Liver Neoplasms; Lung Neoplasms; Male; Mesna; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Palliative Care; Pelvic Neoplasms; Remission Induction; Retrospective Studies; Sarcoma; Soft Tissue Neoplasms; Survival Rate; Vincristine; Young Adult

Hemangiopericytoma (HPC) is a soft-tissue neoplasm composed of proliferating capillary pericytes. It has variable and unpredictable malignancy and most commonly occurs in the fifth or sixth decade of life. Diagnosis is based on the histological aspect. HPC is exceedingly rare in childhood. In both adults and children, curative surgery is the most important predictor of survival. The place of chemotherapy in the treatment of HPC is not well established. We describe a case of adult-type metastatic HPC of the thigh in a 13-year-old boy. The response to neoadjuvant chemotherapy was excellent, and local control of this initially unresectable tumor was achieved without radiation therapy or mutilating surgery. The child is alive and well and has had 8 years of follow-up after treatment.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Dacarbazine; Doxorubicin; Femoral Neoplasms; Hemangiopericytoma; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

To assess the role of consolidative radiation therapy (CRT) in conjunction with myeloablative therapy with or without total body irradiation (TBI) in children and young adults with metastatic or recurrent sarcoma.. Twenty-one pediatric sarcoma patients with metastatic (10) or recurrent (11) disease were entered on a prospective feasibility study of intensive myeloablative therapy with or without TBI. Median patient age was 17.8 years (range, 9.4-24.7 years). Primary histologies included Ewing's (12), PNET (3), and other soft tissue sarcomas (6). Twenty patients received induction chemotherapy. Myeloablative therapy consisted of TBI in 11 patients with either high dose melphalan/etoposide (9) or high dose cytoxan/thiotepa (2). TBI consisted of 12 Gy in 2 Gy fractions delivered twice daily over 3 days. Ten patients received high dose chemotherapy alone, either with thiotepa/carboplatinum/etoposide (8) or cytoxan/carboplatinum (2). Myeloablative therapy was followed by autologous stem cell rescue (ASCR) 24 to 48 hours after completing chemotherapy. Fourteen patients (67%) received CRT either prior to (5) or following (9) myeloablative therapy. Median CRT dose was 37.2 Gy (range, 20-60). Fifty-one disease sites were present prior to myeloablative therapy. Twelve (24%) were bulky (> 8 cm) and 18 (35%) underwent surgical debulking. The median follow-up of surviving patients was 15 months (range, 8-20) with 25% of patients having been followed for more than 20 months.. The 3-year actuarial disease-free (DFS) and overall survival (OS) rates for the entire group were 36% and 27%, respectively. Following myeloablative treatment, responses were: 11 complete, 6 partial, 1 stable, and 3 progressive disease. Sixteen patients (71%) have relapsed. The most common site of relapse was the lung (13). Of the 51 disease sites present prior to myeloablative therapy, 36 sites (71%) were amenable to CRT. Nonamenable sites were: multiple lung metastases (13) and bone marrow (2). Twenty-six amenable sites (51%) received CRT either prior to (14) or following (12) ASCR. Amenable sites treated with CRT had a better 3-year actuarial local control (80 vs 37%) (p = 0.0065) than amenable sites not treated with CRT. Factors associated with improved disease-free survival (DFS) in univariate analysis were induction chemotherapy response (p = 0.002) and extent of surgical resection (p = 0.045). There was a trend toward improved DFS on univariate analysis with the use of TBI as part of myeloablative therapy (p = 0.07). The one factor associated with improved OS on univariate analysis was induction chemotherapy response (p = 0.007). Multivariate analysis revealed that induction chemotherapy response is the only factor that remains significant for DFS (p = 0.032) as well as for OS (p = 0.017). Patients with complete response to induction therapy had 40% probability of survival versus all other patients who had 10% survival (p = 0.05).. Consolidative radiotherapy is feasible in primary metastatic or recurrent pediatric sarcoma patients treated with myeloablative therapy with or without TBI. CRT to sites amenable to irradiation provided an improved 3-year actuarial local control than that seen in sites amenable to CRT that did not undergo radiotherapy. There was a trend for improved DFS with the use of TBI. Improved DFS and OS can be predicted by response to induction therapy. This intensive regimen may improve the cure rate of advanced pediatric sarcomas in select patients.

Topics: Adolescent; Adult; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Bone Neoplasms; Child; Cyclophosphamide; Dactinomycin; Feasibility Studies; Female; Hematopoietic Stem Cell Transplantation; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Neoplasm Recurrence, Local; Prognosis; Prospective Studies; Radiotherapy Dosage; Retrospective Studies; Salvage Therapy; Sarcoma; Treatment Failure; Vincristine; Whole-Body Irradiation

To evaluate the impact of granulocyte colony-stimulating factor (G-CSF) priming on peripheral-blood cell counts during standard-dose chemotherapy.. Twelve patients with relapsed small-cell lung carcinoma (SCLC) were treated with two chemotherapy courses. Six patients received G-CSF priming only before the first course (group A) and the other six patients only before the second course (group B). Each patient served as his own control. Patients were treated with cyclophosphamide, epirubicin, and etoposide (CEE), or with vincristine, ifosfamide, mesna, and carboplatin (VIMP) every 4 weeks. G-CSF was administered subcutaneously 5 microg/kg/d for 6 days until 48 hours before the first or second chemotherapy course.. Priming caused a lowering of the WBC nadir, with a median value of 0.95 x 10(9)/L (P = .004), and of absolute neutrophil nadir, with a median value of 0.48 x 10(9)/L (P = .03). There was a trend for a lower platelet (PLT) nadir after G-CSF priming (P = .09). G-CSF priming resulted in a prolonged duration of WBC count less than 3.0 x 10(9)/L of +4.25 days (P = .04), and of WBC count less than 1.0 x 10(9)/L of +0.50 days (P = .03). The duration of neutropenia less than 0.5 x 10(9)/L seemed longer in primed courses (+3.75 days, P = .18). The duration of PLT counts less than 100 x 10(9)/L was prolonged by 1.5 days (P = .04). Hemoglobin (Hgb) levels were not influenced by G-CSF priming.. G-CSF administration until 48 hours before the next chemotherapy course increases chemotherapy-associated leukocytopenia and thrombocytopenia. This may be of special concern when G-CSF is administered during dose-densified chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carboplatin; Carcinoma, Small Cell; Cyclophosphamide; Epirubicin; Etoposide; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Lung Neoplasms; Mesna; Prospective Studies; Recombinant Proteins; Vincristine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Etoposide; Female; Forearm; Hemangiopericytoma; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Neoplasm Recurrence, Local; Salvage Therapy; Thoracic Neoplasms

We report the case of a patient with a rare miliary variant of osteosarcoma associated with symptomatic hypocalcemia and review the literature regarding the pathogenesis of multifocal osteosarcoma, treatment options, and the associated hypocalcemia.

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Doxorubicin; Expectorants; Fatal Outcome; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Humans; Hypocalcemia; Ifosfamide; Lung Neoplasms; Mesna; Osteosarcoma

From January 1990 to December 1995 we treated 35 patients (pts) with bone and soft tissue sarcoma with ifosfamide (IFM). Sixteen patients had measurable metastatic pulmonary lesion and 9 had primary lesion. Histology of the tumor included osteosarcoma in 13 pts, Ewing sarcoma in 5 pts, malignant fibrous histiocytoma of bone in 2 pts, synovial sarcoma in 7pts, primitive neuroectodermal tumor in 2 pts, and other in 7 pts. The IFM at the dose of 12-18g/m2 (mean 15. 4g/m2) for 5 to 8 days continuous infusion was administered to patients in each treatment course. The uroprotector, mesna, was also given concomitantly in 60-100% dose of IFM. Eighteen pts received one course of IFM treatment. Other pts received 2 to 8 courses of IFM treatment at three to four week intervals. The overall response rate was 40% (PR in 14 pts, NC in 18 pts, and PD in 3 pts). The response rate of 13 pts with osteosarcoma was 54% (PR in 7 pts) and 30% in 15 pts with soft tissue sarcoma (PR in 5 pts).

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Bone Neoplasms; Child; Drug Administration Schedule; Female; Histiocytoma, Benign Fibrous; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Osteosarcoma; Sarcoma; Sarcoma, Ewing; Soft Tissue 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

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

The objective of this prospective study was to evaluate the mortality and morbidity of sarcoma pulmonary metastasis resection with continuous chemotherapy. Ifosfamide was administered at the daily dose of 1200 mg/m2/24 h. Twenty-six resections of pulmonary sarcoma were performed from December 1990 to April 1992. The primary lesion was already resected in all patients. Peri-operatory chemotherapy was started 30 minutes before surgery and continued for 6 days. Chemotherapy was associated with an uroprotector, antiemetic drugs and adequate hydration. Patients had a mean age of 30.6 years. The delay between initial and thoracic surgery was 81 months. The following was performed: tumorectomy (32), wedge (18), lobectomy (7), diaphragm resection (1), left pneumectomy (1). All patients had the 6-days chemotherapy course. None of the patients died. Respiratory failure following superinfection, but not necessitating assisted ventilation, was observed in one case. The following adverse events were noted: nausea (34.6%), uncomplicated cystitis (15.4%), leucopenia (7.6%), fever (3.8%). Mean duration of hospitalization was 11.8 days. Chemotherapy adverse effects did not result in significant morbidity. Bronchial fistula was not observed. Following the results of this pilot study, we feel that perioperatory chemotherapy can be added to sarcoma pulmonary metastasis resection surgery without increasing patient morbidity and mortality.

Topics: Adult; Combined Modality Therapy; Female; Humans; Ifosfamide; Infusions, Intravenous; Intraoperative Period; Lung Neoplasms; Male; Mesna; Ondansetron; Prospective Studies; Sarcoma; Survival Analysis

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

The prognostic value of serum neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) was prospectively assessed in 42 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated within two chemotherapy trials. Pretreatment NSE levels ranged from 4.6 to 34.6 ng/mL (median value, 7.5) and were above 10 ng/mL in ten patients (23.8%). LDH levels varied between 85 U/L and 2,484 U/L (median value, 220) and were above 250 U/L in 12 patients (29.3%). Elevated levels of both enzymes were significantly more common in patients with metastatic disease than in those with locoregional disease (40% v 9% for NSE and 40% v 18% for LDH, respectively). Strong positive correlation (correlation factor 0.693) was found between NSE and LDH serum levels. The levels of both markers did not correlate with age, sex, previous therapy, performance status, or histology. Responses to chemotherapy were seen more frequently in patients with elevated NSE levels (six of ten, 60%) than in those with normal values (seven of 32, 22%; P = .02). Similar correlation was found for LDH: Response was seen in seven of 12 patients with elevated levels (58%) and in six of 29 (21%) of those with normal values (P = .02). In a logistic regression analysis, both markers considered individually remained significant when adjusted by sex, age, performance status, prior therapy, histology, and extent of disease. Three pretreatment characteristics, high levels of NSE and LDH (both considered as continuous variables) and metastatic disease, were found to be associated with shorter survival; with adjustment for extent of disease, however, NSE and LDH were no longer correlated with shorter survival. These data suggest potential clinical value of NSE and LDH determination in treatment selection of NSCLC patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Carcinoma, Non-Small-Cell Lung; Etoposide; Female; Humans; Ifosfamide; L-Lactate Dehydrogenase; Lung Neoplasms; Male; Mesna; Middle Aged; Phosphopyruvate Hydratase; Probability; Prospective Studies; Remission Induction; Survival Rate

The purpose of this study was to evaluate the toxicity and response efficacy of fixed-dose oral ifosfamide (OI)-mesna (M) in advanced, non-small-cell lung cancer (NSCLC). OI was given in four different fractionated-dose treatment schedules with a total dose per cycle of either 3.0 g/m2, 6.0 g/m2, 7.5 g/m2 or 10 g/m2 (equivalent to a daily dose of either 750 mg, 1000 mg or 1250 mg.) M was given p.o. by drinking ampules. In the 64 patients (pts) included, a total of 305 treatment cycles were administered with no evidence of severe neurotoxicity. Twenty-two pts (37%) developed mild to moderate CNS toxicity. Neither myelosuppression, alopecia, gastrointestinal toxicity nor urotoxicity were clinical problems. On schedule 2 (6 g/m2), 3 of 14 evaluable pts (21%) had partial remissions (PR), and on schedule 3 (7.5 g/m2) 4 pts (25%) showed PRs. The median duration of response was 9 months (mts) for pts on schedule 2, and 8 mts for pts on schedule 3. We conclude that OIM can easily be tolerated in the same dose usually given intravenously (7.5 g/m2/mts), when patients at high risk for developing CNS toxicity have been previously excluded from therapy. In order to reduce CNS toxicity, it is suggested that the total dose per cycle should not exceed 7.5 g/m2 (1000 mg daily) within a fractionated-dose, 14-day treatment schedule. We further conclude that the tumor response efficacy of OIM in NSCLC is comparable to the one achieved by intravenously-administered IM, whereby the total monthly OI dose should not be less than 6.0 g/m2 (750 mg daily).

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Dreams; Drug Administration Schedule; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasm Staging; Remission Induction; Sleep Wake Disorders

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

The mesna, doxorubicin, ifosfamide, dacarbazine regimen produced a 47% response rate (including 10% complete responses) in 105 eligible adults with advanced sarcoma. The major dose-limiting toxicity was granulocytopenia. There was one toxic death from sepsis. Central nervous system and renal toxicity occurred infrequently, perhaps as a result of the continuous-infusion schedule. This regimen is being evaluated further in advanced disease, the adjuvant setting, and in combination with bone marrow colony-stimulating factors.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Combined Modality Therapy; Dacarbazine; Doxorubicin; Drug Evaluation; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Remission Induction; Sarcoma; Survival Rate

Ifosfamide and cyclophosphamide have many toxicities in common. Interstitial pneumonitis has not been reported previously as a side effect of ifosfamide therapy. The authors report the case of a 58-year-old woman who was treated with ifosfamide for soft tissue sarcoma. After the fifth cycle of chemotherapy she developed clinical evidence of interstitial pneumonitis, a diagnosis that was later confirmed at autopsy. The authors suggest that ifosfamide therapy was directly related to this patient's fatal case of interstitial pneumonitis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Female; Humans; Ifosfamide; Lung Neoplasms; Mesna; Middle Aged; Pulmonary Fibrosis; Sarcoma

Carboplatin, a clinically active analogue of cisplatin, was added to a regimen containing ifosfamide and etoposide, two agents with proven activity in non-small cell lung cancer (NSCLC). From August 1986 until November 1988, 43 consecutive patients (29 men and 14 women), mean age 57 years, performance status of 2 or less, with symptomatic, inoperable NSCLC were accrued and received carboplatin 100 mg/m2 on days 1, 3, and 5, or 300 or 350 mg/m2 on day 1; ifosfamide 1,500 mg/m2 and etoposide 60 or 100 mg/m2 every 4 weeks. Thirty-four patients were previously untreated, nine had been irradiated before, and two had also received previous chemotherapy. So far, 154 courses have been administered; 19 patients have received four or more courses. With the combination of 350 mg/m2 carboplatin and 100 mg/m2 etoposide, myelosuppression was dose-limiting; nephrotoxicity and neurotoxicity did not occur. Evaluation of response after two or four courses in 40 patients showed an objective response in 40%, whereas 30% progressed during therapy. Carboplatin added to etoposide and ifosfamide is a feasible combination that warrants further study in a randomized fashion.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Organoplatinum Compounds; Survival Rate

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.

Topics: Aged; Carcinoma, Bronchogenic; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Middle Aged; Survival Rate; Urologic Diseases; Vincristine

Fifty patients with histologically confirmed advanced malignancies were treated with ifosfamide and mesna plus other cytostatics. The other cytostatic drugs added to the treatment regimen were cisplatin (36 pts), etoposide (31 pts) and doxorubicin (20 pts). Among previously untreated patients objective response was documented in 12 of 19 pts with ovarian cancer, 9 of 14 with small cell cancer of the lung and in all 3 pts with Ewing's sarcoma. Among patients with disease refractory to prior cytostatic treatment, objective response was documented in 8 of 9 with testicular cancer, 1 of 3 with high grade lymphoma and 0 of 2 with osteosarcoma. Side-effects due to the combination of ifosfamide plus mesna and other cytostatics were acceptable. No life-threatening or lethal toxicities occurred. Most commonly encountered toxicities were leukopenia (64%), nausea and vomiting (84%), alopecia (63%), CNS toxicity (30%) and renal toxicity (12%).

Topics: Adolescent; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Cisplatin; Etoposide; Female; Humans; Ifosfamide; Leukopenia; Lung Neoplasms; Male; Mesna; Middle Aged; Nausea; Ovarian Neoplasms; Sarcoma, Ewing; Testicular Neoplasms; Vomiting

Ifosfamide and mitomycin C are two of the more active single agents in non-small-cell lung cancer (NSCLC). This study evaluates these drugs in combination followed by radiotherapy. A total of 33 ambulatory patients with inoperable NSCLC were treated with 5 g/m2 ifosfamide as a 24-h infusion, with the concurrent administration of sodium 2-mercaptoethane sulphonate (mesna; 160% of the ifosfamide dose) and 6 mg/m2 mitomycin C given as an i.v. bolus injection on the 2nd day. The median age of the patients was 61 years. In all, 20 patients had limited disease and 13, extensive disease. A total of 30 were assessable for response to chemotherapy, 8 of whom achieved a partial response (PR) and 5, a complete response (CR) (2 were verified bronchoscopically). The overall response rate was thus 43%. All but one response (a PR) were in patients with limited disease (LD). A total of 21 patients, including 13 responders, received thoracic irradiation (30 Gy in 8 fractions over 10 days) following chemotherapy. One PR was converted to a radiological CR. In all, 17 (55%) of the patients were alive at 1 year. All patients suffered chemotherapy-induced alopecia (WHO grade 3), but there were no treatment modifications due to myelosuppression, haemorrhagic cystitis or other toxicity. WHO grade 3 nausea and vomiting were seen in all patients. There was one treatment-related death. Combination therapy using ifosfamide and mitomycin C has useful activity in NSCLC.

Topics: Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Drug Evaluation; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Mitomycins; Nausea; Remission Induction; Vomiting

The pharmacokinetics of intravenous ifosfamide were determined in 16 patients with carcinoma of the bronchus. In all 25% (4) of these patients were obese (i.e. greater than 20% over their ideal body weight). The terminal elimination half-life (t1/2 beta) was found to be higher in the obese group than in the control group (6.36 h, range 5.77-7.45 h) vs 4.95 h, range 1.82-6.48 h) (P less than 0.05). This prolongation of the elimination half-life was due to an increased volume of distribution (Vd beta) in the obese group (42.81 1, range 35.49-51.90 l) vs 33.70 l range (17.76-50.62 l) (P less than 0.05). There was therefore no significant difference in total plasma clearance between the obese and normal groups. No correlation of ifosfamide plasma half-life was observed with total body weight (TBW) or ideal body weight (IBW). However, a significant positive correlation was observed between the percentage of IBW and plasma half-life. A strong positive correlation was observed between IBW and the plasma clearance of ifosfamide. The Vd beta correlated with both TBW and the percentage of IBW, but not with IBW itself. When Vd beta was normalised for IBW, there was a strong positive correlation with the percentage of IBW, suggesting that ifosfamide distribution into the TBW is higher than that into the IBW.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chromatography, High Pressure Liquid; Half-Life; Humans; Ifosfamide; Lung Neoplasms; Mesna; Middle Aged; Obesity; Time Factors; Tissue Distribution

Twelve patients with advanced small cell carcinoma of the bronchus were treated by continuous infusion of recombinant human granulocyte colony-stimulating factor (rh G-CSF) at the following dose levels: 1 microgram, 5 micrograms, 10 micrograms, 20 micrograms and 40 micrograms/kg/day for 5 days. No toxicities resulted from the treatment and in all 12 patients the number of peripheral neutrophils increased rapidly to a maximum of 100 x 10(9)/l in one patient at 10 micrograms/kg/day. The neutrophils were shown to be functionally normal in tests of their mobility and bactericidal activity. During the Phase II part of the patients were treated using a combination of i.v. Adriamycin, Ifosfamide and Etoposide. The chemotherapy was repeated every 3 weeks. rh G-CSF was given to each patient for 14 days on alternate cycles of chemotherapy and reduced the period of absolute neutropenia considerably (median of 80%), with a return to normal, or above normal, neutrophil counts within 2 weeks after day 1 of chemotherapy. Ten severe infective episodes were observed during the 20 cycles of chemotherapy which did not include rh G-CSF, while only one infective episode occurred in 20 courses when treated with rh G-CSF. These results demonstrate the utility of rh G-CSF in restoring functional neutrophils to patients undergoing intensive chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Colony-Stimulating Factors; Doxorubicin; Drug Evaluation; Etoposide; Granulocyte Colony-Stimulating Factor; Hemoglobins; Humans; Ifosfamide; Leukocyte Count; Lung Neoplasms; Mesna; Neutrophils; Platelet Count; Recombinant Proteins

Eight-eight previously untreated patients with small cell lung cancer were treated with a combination of VP16, adriamycin and vincristine (VPAV) for three courses. Resistance to these drugs is associated with the multidrug resistance (MDR) membrane glycoprotein in cell lines in vitro. The clinical relevance of this mechanism of resistance was assessed by using a second line treatment with intravenous infusions of ifosfamide/mesna 5 g/m2 every 3 weeks in patients with only partial responses or non-responders. Cross-resistance to alkylating agents is rare in the MDR. Ifosfamide produced partial responses in six (43%) of 14 patients unresponsive to prior therapy. Intravenously infused ifosfamide/mesna was also used in consolidation therapy with only minor bone marrow or urinary tract toxicity. This did not prevent CNS relapse. The overall response rate to VPAV was 69% and for all treatment modalities, 75%. Median survival for all patients ws 39.5 weeks and 59 weeks for all patients attaining complete response. The addition of large fraction chest irradiation given with the final course of induction chemotherapy to those with good chemotherapy responses produced a further response in 44% of assessable patients. Combined modality treatment resulted in moderate and reversible toxicity. The lack of improved survival with ifosfamide and the resistance of the majority of patients to salvage with ifosfamide/mesna suggested that the MDR is not the major mechanism of resistance in the clinic, since cross-resistance to alkylating agents of this type is not a feature of MDR cells.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Combined Modality Therapy; Doxorubicin; Drug Resistance; Etoposide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Vincristine

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Evaluation; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged

Topics: Adult; Aged; Carcinoma, Small Cell; Carmustine; Combined Modality Therapy; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged

Topics: Adult; Aged; Carcinoma, Bronchogenic; Female; Hematuria; Humans; Ifosfamide; Lung Neoplasms; Lymphoma, Non-Hodgkin; Male; Mercaptoethanol; Mesna; Middle Aged; Neoplasms; Ovarian Neoplasms; Testicular Neoplasms

One hundred sixty-three patients with small cell lung cancer were treated with six courses, at 3-week intervals, of ifosfamide (5 g/m2) with mesna and etoposide. Thoracic radiotherapy was delivered to the limited stage (LS) patients. The complete response rate (CR, determined clinically and radiologically) was 76% for the 78 LS patients with a further 14% partial response (PR). The majority of the CRs were confirmed on a follow-up bronchoscopy. The CR rate was 27% for extensive stage (ES) patients with another 38% undergoing a partial response. The median survival for LS patients was 11 months, (16 months for CR confirmed by rebronchoscopy) and 8 months for ES patients. The 2-year actuarial survival for LS patients is 27%, follow-up ranges from 12 months to 30 months with a median of 22 months. Toxicity was not severe for the patient population, of whom only 20% had a good performance status before chemotherapy. Parental antibiotics were required on 4% of all 844 chemotherapy courses and 12% of courses were delayed due to side effects. The majority of responses occurred within the first two courses of chemotherapy and there was a corresponding improvement in the patients' symptoms and performance status. The regimen produced rapid tumor response with corresponding improvement in symptoms without marked toxicity and allowed further treatment development.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Combined Modality Therapy; Etoposide; Evaluation Studies as Topic; Female; Humans; Ifosfamide; Lorazepam; Lung Neoplasms; Male; Mesna; Metoclopramide; Middle Aged

Thirty-two evaluable patients with stage III non-small cell lung cancer were treated with the combination of ifosfamide (4 g/m2), with uroprotective mesna, mitomycin (6 mg/m2), and cisplatin (100 mg/m2). The overall response rate was 68.8% (complete response rate, 21.9%; partial response rate, 46.9%). Toxicity was moderate and manageable. Based on the response rate observed, this three-drug combination could be considered for future randomized phase III trials against non-small cell lung cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Evaluation; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Mitomycins; Remission Induction

Following therapeutic administration, cyclophosphamide and Adriamycin are biotransformed to reactive metabolites, some of which are responsible for undesirable systemic toxicities of these chemicals, whereas others are responsible for their chemotherapeutic effectiveness. Microsomal mixed function oxidases activate cyclophosphamide to produce phosphoramide mustard and acrolein, while cytochrome reductase and xanthine oxidase are capable of transforming Adriamycin and forming free radicals. These reactive metabolites produce unwanted toxic side effects; however, their action may be partially ameliorated by the concomitant administration of thiols. In this study we evaluated the therapeutic activity of combinations of mesna (2-mercaptoethanesulfonate) with cyclophosphamide or Adriamycin in mice with a variety of transplantable tumors (L1210 and P-388 leukemia, Lewis lung and colon 26 carcinoma, B16 melanoma, and M5076 sarcoma). In all cases the administration of mesna prior to cyclophosphamide or Adriamycin treatment did not reduce the antitumor effectiveness of these agents and in some instances (C57BL/6 mice with B16 melanoma or M5076 sarcoma) small improvements were observed. Therefore, the addition of thiols, to reduce effectively the buildup of toxic metabolites of cyclophosphamide or Adriamycin may result in the improved therapeutic effectiveness for these agents in the treatment of cancer.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Cyclophosphamide; Doxorubicin; Female; Leukemia, Experimental; Lung Neoplasms; Melanoma, Experimental; Mercaptoethanol; Mesna; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Sarcoma, Experimental

A combination of vindesine (3 mg/m2, day 1) and ifosfamide (60 mg/kg, days 1-5 + Mesna) was administered every three weeks to 11 patients with primary resistant and 23 with recurrent small-cell bronchial carcinoma. All patients had been pre-treated with chemotherapy, 16 in addition with radiotherapy. At the onset of the vindesine-ifosfamide treatment the cancer was in a localized regional stage in ten patients, while in 24 it was in a more widely spread stage. In 29 patients whose treatment results could be evaluated the remission rate was 38%, with two complete and nine partial remissions. In a further eight patients the cancer was arrested. The patients with complete remission (for 46 and 53 weeks, respectively), those with partial remission (median of 39 weeks) and those with stationary disease (median of 31 weeks) survived significantly longer than those with progressing disease (13 weeks). There was no correlation between treatment result and pre-treatment. On recurrence after complete remission or in the localized regional stage the remission rate was 70% and 60%, respectively, and the survival time was extended in 90% of cases. In addition to nausea, alopecia and myelosuppression, side-effects included vomiting, reversible CNS symptoms, polyneuropathy and urotoxicity. On the basis of acceptable toxicity, combined vindesine and ifosfamide constitute an effective treatment of otherwise treatment-refractory cases of small-cell bronchial carcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Drug Administration Schedule; Humans; Ifosfamide; Lung Neoplasms; Male; Mesna; Middle Aged; Neoplasm Recurrence, Local; Vindesine

Ifosfamide at 5 g/m2 was given as a bolus to 48 patients with advanced progressing non-small cell lung cancer. Mesna (5 g/m2) was also given with the ifosfamide, both over 30 min. Further mesna was then given p.o. (3 g/m2) at 4, 8, and 12 h. If oral mesna was not acceptable then one or, if necessary, two 4-h to 6-h infusions (3 g/m2) were administered. A maximum of six courses at 3-weekly intervals was prescribed. A total of 174 courses was administered, and oral mesna was given during 64 courses: discharge was considered possible within 8-10 h after 55% of courses. Haematological toxicity was mild and no renal dysfunction was noted. Two patients became drowsy shortly after ifosfamide, but recovered 24-36 h later. The objective response rate was 29%, with one complete responder. A further 31% of patients (symptomatic responders) with stable disease symptomatically improved after the chemotherapy, by 20 or more points on the Karnofsky scale. The median survival was 5 months for the whole group, and 8 months each for the objective and symptomatic responder groups. Most patients' Karnofsky and respiratory scores improved with the chemotherapy. Ifosfamide with mesna can be given by short infusions, and the mesna given p.o. prevents any urothelial toxicity. Further exploration of short-infusion ifosfamide and mesna therapy would reduce hospitalization and allow for day-case regimens.

Topics: Adult; Aged; Carcinoma, Small Cell; Drug Administration Schedule; Female; Humans; Ifosfamide; Injections, Intravenous; Lung Neoplasms; Male; Mesna; Middle Aged

Topics: False Positive Reactions; Female; Humans; Ifosfamide; Ketone Bodies; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Middle Aged

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

Topics: Brain Diseases; Carcinoma, Small Cell; Cyclophosphamide; Female; Humans; Ifosfamide; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Middle Aged; Sarcoma

The influence of sodium-2-mercaptoethanesulphonate (Mesna) on urinary bladder cancer induced by N-nitroso-N-butyl-N-(4-hydroxybutyl)amine (BBNOH) was studied in male Sprague-Dawley rats. The treatment consisted of 5 g/kg BBNOH per gavage and 63 g/kg Mesna in drinking water over a period of 39 weeks. A positive control group was given the same dose of BBNOH as the treated group. Although Mesna did not reduce the incidence of bladder carcinomas, it significantly increased the lifespan of the animals, thus suggesting a partial general protective action.

Topics: Animals; Body Weight; Butylhydroxybutylnitrosamine; Carcinogens; Drinking; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Nitrosamines; Rats; Rats, Inbred Strains; Time Factors; Urinary Bladder Neoplasms

Topics: Adult; Aged; Carcinoma, Small Cell; Cyclophosphamide; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Mercaptoethanol; Mesna; Middle Aged

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Bronchogenic; Cyclophosphamide; Doxorubicin; Humans; Ifosfamide; Lung Neoplasms; Mercaptoethanol; Mesna