mesna and Carcinoma--Non-Small-Cell-Lung

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

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

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

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

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

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

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

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

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

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

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

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

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

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