Glutathione-S-transferase P1 isoenzyme polymorphisms, platinum-based chemotherapy, and non-small cell lung cancer.

BACKGROUND: Polymorphisms within the P1 isoenzyme of GST (GSTP1) are associated with alterations in enzyme activity and may change sensitivity to platinum-based chemotherapy. We investigated the relationship between exon 5 and exon 6 GSTP1 gene polymorphisms and treatment response, hematological, and nonhematological toxicity and overall survival for patients receiving platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC). METHODS: Between 2001 and 2002, 108 patients with chemotherapy-naïve advanced NSCLC were recruited. Associations between the GSTP1 polymorphisms (Ile105Val, Thr110Ser, Ala114Val, and Asp 147Tyr) and GSTP1*A, *B, and *C haplotypes and treatment response and toxicity were evaluated using the Pearson chi and Kruskal-Wallis tests, respectively. Associations with survival were compared using Kaplan-Meier survival curves and Cox proportional hazard ratios. RESULTS: No significant associations were noted between GSTP1 polymorphisms and treatment response or survival. Significantly less neutropenic toxicity was demonstrated for patients possessing the 105Val allele (p = 0.020) or the GSTP1*B haplotype (p = 0.038). However, the variant allele GSTP1 105Val, and patients possessing a GSTP1*B allele demonstrated notable trends toward inferior response and survival. CONCLUSIONS: GSTP1 haplotype can be used to stratify hematological toxicity after platinum-based chemotherapy, but the lack of significant associations with response or survival suggests that GSTP1 polymorphisms may not be strong pharmacogenomic markers in this population. Additional large prospective studies incorporating the GSTP1 haplotype may clarify the reported discrepancies.

Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: The authors compared gemcitabine and carboplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) or mitomycin, vinblastine, and cisplatin (MVP) in patients with advanced nonsmall cell lung carcinoma (NSCLC). The primary objective was survival. Secondary objectives were time to disease progression, response rates, evaluation of toxicity, disease-related symptoms, World Health Organization performance status (PS), and quality of life (QoL). METHODS: Three hundred seventy-two chemotherapy-naïve patients with International Staging System Stage III/IV NSCLC who were ineligible for curative radiotherapy or surgery were randomized to receive either 4 cycles of gemcitabine (1000 mg/m(2) on Days 1, 8, and 15) plus carboplatin (area under the serum concentration-time curve, 5; given on Day 1) every 4 weeks (the GC arm) or MIC/MVP every 3 weeks (the MIC/MVP arm). RESULTS: There was no significant difference in median survival (248 days in the MIC/MVP arm vs. 236 days in the GC arm) or time to progression (225 days in the MIC/MVP arm vs. 218 days in the GC arm) between the 2 treatment arms. The 2-year survival rate was 11.8% in the MIC/MVP arm and 6.9% in the GC arm. The 1-year survival rate was 32.5% in the MIC/MVP arm and 33.2% in the GC arm. In the MIC/MVP arm, 33% of patients responded (4 complete responses [CRs] and 57 partial responses [PRs]) whereas in the GC arm, 30% of patients responded (3 CRs and 54 PRs). Nonhematologic toxicity was comparable for patients with Grade 3-4 symptoms, except there was more alopecia among patients in the MIC/MVP arm. GC appeared to produce more hematologic toxicity and necessitated more transfusions. There was no difference in performance status, disease-related symptoms, or QoL between patients in the two treatment arms. Fewer inpatient stays for complications were required with GC. CONCLUSIONS: The results of the current study failed to demonstrate any difference in efficacy between the newer regimen of GC and the older regimens of MIC and MVP. Cancer 2003;98:542-53.

Phase II study of three-dimensional conformal radiotherapy and concurrent mitomycin-C, vinblastine, and cisplatin chemotherapy for Stage III locally advanced, unresectable, non-small-cell lung cancer.

PURPOSE: To evaluate the feasibility, treatment outcome, and toxicity of hyperfractionated three-dimensional conformal radiotherapy (CRT) and concurrent mitomycin-C, vinblastine, and cisplatin (MVP) chemotherapy in locally advanced, unresectable, Stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Between August 1993 and December 1996, 161 patients with unresectable Stage III NSCLC were entered into this trial, and 146 (91%) completed the treatment. Hyperfractionated RT was given to a total dose of 64.8-70 Gy (1.2 Gy/fraction, b.i.d.) with two cycles of concurrent MVP chemotherapy (mitomycin-C 6 mg/m(2) on Days 2 and 29, vinblastine 6 mg/m(2) on Days 2 and 29, and cisplatin 60 mg/m(2) on Days 1 and 28). Of the 146 patients who completed the treatment, 78 received noncoplanar three-dimensional CRT using 4-6 fields and 17 received coplanar-segmented CRT. The clinical tumor response was assessed 1 month after RT completion by CT. Toxicity was graded using the Southwestern Oncology Group criteria. The normal tissue complication probability for the lung was calculated to determine the correlation with radiation pneumonitis, if any. Nineteen (13%) had Stage IIIA and 127 (87%) had IIIB disease, including 16 patients with pleural effusion and 20 with supraclavicular lymph node metastasis. RESULTS: The response rate was 75%, composed of 22% complete responders and 53% partial responders. With a minimal follow-up of 45 months, the overall survival rate was 51.2% at 1 year, 25.1% at 2 years, and 14.8% at 5 years; the median survival was 12 months. Patients achieving a complete response (n = 32) had a 2-year overall survival rate of 49.8% and a 5-year survival rate of 39.2% compared with 22.5% and 11.4%, respectively, for the partial responders (n = 78; p = 0.0001). The actuarial local progression-free survival rate for all patients was 65.4% at 1 year, 42.1% at 2 years, and 36.3% at 4 years, and the actuarial distant-free survival rate was 65.4% at 1 year, 42.1% at 2 years, and 36.2% at 5 years. Severe weight loss (>10%) occurred in 20 (13.7%) of the 146 patients during treatment, 42 patients (29%) developed radiation pneumonitis (29 Grade 1 and 13 Grade 2). The average normal tissue complication probability value of the patients who had radiation pneumonitis was significantly greater than that of patients without pneumonitis (66.0% vs. 26.4%). Four patients died of treatment-related toxicity. CONCLUSION: Hyperfractionated three-dimensional CRT and concurrent chemotherapy, as described here, is a well-tolerated regimen with acceptable toxicity. More effective treatment schemes are required to improve local disease control and overall survival.

Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer.

PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) (ECF) with the combination of mitomycin, cisplatin, and PVI 5-FU (MCF) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Five hundred eighty patients with adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma were randomized to receive either ECF (epirubicin 50 mg/m(2) every 3 weeks, cisplatin 60 mg/m(2) every 3 weeks and PVI 5-FU 200 mg/m(2)/d) or MCF (mitomycin 7 mg/m(2) every 6 weeks, cisplatin 60 mg/m(2) every 3 weeks, and PVI 5-FU 300 mg/m(2)/d) and analyzed for survival, response, toxicity, and quality of life (QOL). RESULTS: The overall response rate was 42.4% (95% confidence interval [CI], 37% to 48%) with ECF and 44.1% (95% CI, 38% to 50%) with MCF (P =.692). Toxicity was tolerable, and there were only two toxic deaths. ECF resulted in more grade 3/4 neutropenia and grade 2 alopecia, but MCF caused more thrombocytopenia and plantar-palmar erythema. Median survival was 9.4 months with ECF and 8.7 months with MCF (P =.315); at 1 year, 40.2% (95% CI, 34% to 46%) of ECF and 32.7% (95% CI, 27% to 38%) of MCF patients were alive. Median failure-free survival was 7 months with both regimens. Global QOL scores were better with ECF at 3 and 6 months. CONCLUSION: This study confirms response, survival, and QOL benefits of ECF observed in a previous randomized study. The equivalent efficacy of MCF was demonstrated, but QOL was superior with ECF. ECF remains one of the reference treatments for advanced esophagogastric cancer.

Induction of sister chromatid exchanges and chromosome aberrations in cultured mammalian cells treated with aminophenylnorharman formed by norharman with aniline.

Aminophenylnorharman (APNH) is a newly identified mutagenic heterocyclic amine formed by coupling of norharman with aniline in the presence of S9 mix. Furthermore, mutagenic amino-3'-methylphenylnorharman (AMPNH) and aminophenylharman (APH) have been identified from a reaction mixture of norharman and o-toluidine and that of harman and aniline, respectively, with S9 mix. Among these three heterocyclic amines, APNH shows most potent mutagenic activity towards Salmonella typhimurium TA98 and YG1024 with S9 mix. In the present study, the induction of sister chromatid exchanges (SCEs) by APNH was examined in Chinese hamster lung (CHL) cells in vitro, comparing it to those of AMPNH and APH. On incubation with rat S9 for 6h, followed by a recovery culture period of 18h, a dose-dependent effect was found at concentrations between 0.00125 and 0.01 microg/ml for APNH and between 0.3125 and 5 microg/ml for AMPNH and APH. The approximate chemical concentrations leading to a three-fold of control SCE levels calculated from slopes of the linear regressions of induced SCEs were 0.005 for APNH, 0.51 for AMPNH and 1.7 microg/ml for APH. Because of the very strong SCE-causing ability of APNH, we further explored its genotoxicity by examining the induction of chromosome aberrations in CHL cells. A dose-dependent effect was found for chromosome aberrations at concentrations between 0.00125 and 0.04 microg/ml of APNH. The aberrations observed were primarily chromatid exchanges (cte) and breaks (ctb). In conclusion, the potency of SCE induction and clastogenic activity induced by APNH is stronger than Actinomycin D, Mitomycin C (MMC) or 1,8-dinitropyrene which are considered to be the potent clastogens in the literature. Further studies are needed for elucidating mechanisms of the genotoxic actions of these compounds and for evaluating their potential hazards to human health.

[Clinical research of effect of Pill Fufang Zaofan together with radiotherapy and chemotherapy].

OBJECTIVE: To study effect of Pill Fufang Zaofan together with radiotherapy and chemotherapy at same time. METHODS: Treat group administrated Pill Fufang Zaofan from 1 week before radiotherapy and chemotherapy, to 4 weeks after radiotherapy and chemotherapy. Control group didn't administrate Pill Fufang Zaofan. Other agents of two groups are no difference. RESULTS: White blood cells (WBC) of treat group were much more than those of control group. The cases of treat group in which WBC was lower than normal level were obviously less than those of control group. CONCLUSION: Pill Fufang Zaofan can protect bone marrow when using with radiotherapy and chemotherapy at same time.

[Clinical and experimental study on effect of shuanghuang shengbai granule on myelosuppression induced by chemotherapy and ultrastructure observation of bone marrow in mice].

OBJECTIVE: To observe the leukocyte increasing effects of Shaunghuang Shengbai Granule (SHSBG) in tumor patients treated by chemotherapy (CT) and its function on bone marrow hematopoietic microenvironment in mice. METHODS: Patients of non-small-cell lung cancer and breast, gastric or intestinal cancer, who were retreated with CT, were enrolled and divided into 4 groups randomly. The 28 cases in the treated group 1 received SHSBG and CT simultaneously. The 27 cases in the treated group 2 also received firstly CT, and SHSBG started when WBC count lowered to less than 4 x 10(9)/L after CT. The control group 1 and 2 (n = 33 and n = 24) was treated by the method similar to that applied to the treated group 1 and 2 respectively but with Rubidate instead of SHSBG. Experimental study of observing bone marrow ultrastructure in mice was also conducted with electron microscopy. RESULTS: The total leukocyte increasing effective rate occurred in the treated group 1 was 75.00%, that in the treated group 2 was 88.89%, in the control group 1 was 54.55% and in the control group 2 was 58.33%. There was significant difference between the treated groups and the control groups (P < 0.01). Experimental study showed that SHSBG has good bone marrow hematopoietic microenvironmental protecting and improving effect in mice. CONCLUSION: SHSBG has obvious protecting and treating effect on CT caused bone marrow suppression in tumor patients.

In vitro screening of antitumour agents for cardiotoxicity by means of isolated mouse left atria.

Cardiotoxicity, a side-effect that can occur after treatment with an anticancer drug, has severe clinical implications. Therefore, a model is desired to screen new anticancer drugs or drug combinations for possible cardiotoxic side-effects. In the present study we tested the applicability of the electrically stimulated isolated mouse left atrium model using a wide range of anticancer drugs with known cardiotoxicity. It appeared that the cardiotoxicity observed in our model, i.e. the negative or positive inotropic effects of the drugs on the isolated atrium, corresponded with the observed cardiotoxicity in animals and/or humans. It is therefore concluded that our model can be used to wam for possible cardiotoxic side-effects of anticancer drugs in vivo.

Phase I and pharmacologic study of BMS-181174 given as a 6 h infusion every 4 weeks to patients with advanced solid tumors.

BMS-181174, a new mitomycin C (MMC) analog, showed more activity than the parent compound in tumor xenografts. In a phase I study with a 5-30 min slow bolus administration, hematologic and vascular toxicity were observed as major side effects. A prolonged infusion was suggested to circumvent the vascular toxicity. In this phase I study BMS-181174 was administered as a 6 h infusion every 4 weeks; the doses studied were 3.2, 6.4, 11.5, 19.0, 32.0, 50.0, 75.0 and 100 mg/m2. Twenty-eight patients were enrolled in the study, the majority with colorectal cancer. Hematologic side effects consisted of thrombocytopenia, and mild leuko- and granulocytopenia. The most distressing non-hematologic side effect was vascular toxicity consisting of phlebosclerosis and phlebitis, becoming dose limiting at 100 mg/m2. One patient developed a hemolytic uremic syndrome at a cumulative dose of 350 mg/m2. Pharmacokinetic data are available for 24 patients. The AUC ranged from 3.35 to 41.49 (microg x h/ml) and was highly correlated with the dose administered (r = 0.83). The kinetics appeared to be linear. One patient with metastatic colon cancer had a partial response of liver metastases. BMS-181174 is a MMC analog with a toxicity profile comparable to that of the parent compound. As doses above 50 mg/m2 are complicated by vascular toxicity precluding multiple administrations, further exploration of BMS-181174 will not be performed.

KW-2149-induced pulmonary toxicity is not prevented by corticosteroids: a phase I and pharmacokinetic study.

KW-2149 is a new, semisynthetic, C-7-N-Substituted, mitomycin C analog showing antitumor activity both in vitro and in vivo, equal or superior to mitomycin C. In a phase I study, KW-2149 was administered as an i.v. bolus injection every 21 days and at a dose of 100 mg/m2 pulmonary toxicity was dose limiting. Animal studies have indicated since that KW-2149-induced pulmonary toxicity can be prevented by pretreatment with corticosteroids. This paper presents the results of a further phase I study of KW-2149 with corticosteroid pretreatment. Patients were treated with oral dexamethasone 8 mg every 12 h, starting 24 h before KW-2149 administration, for 5 days. KW-2149 was given as an i.v. bolus injection every 21 days. Seventeen patients were treated with a total of 48 courses. Six patients received 60 mg/m2 and 11 patients 75 mg/m2. Two courses were not evaluable for toxicity. Significant lung toxicity was observed in at least three patients treated with a dose of 75 mg/m2 KW-2149 and pulmonary toxicity was therefore considered the dose-limiting toxicity at 75 mg/m2. No other important side effects were noted. One partial response was observed in a patient with colorectal cancer. Pretreatment with dexamethasone failed to suppress KW-2149-induced lung toxicity.

Small bowel permeability in patients with cytostatic therapy.

The purpose of this study was to examine the influence of cytostatic therapy on the barrier function of the small bowel. In 16 patients with tumors in the gastrointestinal tract with metastatic involvement of the liver, small bowel permeability was measured using the lactulose/mannitol test. The patients were treated for 5 d with fluorouracil (750-1000 mg/d) and leucovorin (25-50 mg/d). The examination was performed on the first day, at the beginning of the cytostatic therapy, and also 5, 12, and 28 d after the therapy had begun. In comparing the start and the end of this therapy, the index of permeability was significantly increased (as measured 7 d after the end of therapy). These results show the damage of small bowel barrier after cytostatic therapy.

Uso de la Milamicina C instalada, como profilaxis en la recurrencia de Pterigiones: en pacientes intervenidos quirúrgicamente en el Centro Nacional de Oftalmología

El presente estudio tiene como objetivo identificar el efecto de la Mitomicina C 0.02, instalada en el postoperatorio, en 20 pacientes escogidos al azar, con historias de 1 a 5 recurrrencias de pterigion. Los sujetosdel estudio se intervinieron entre los meses de septiembre y noviembre de 1998, con la técnica de escisión simple. En el primer día postoperatorio cada pacientes inició el uso de Mitomicina C al 0.02, una gota cada 8 horas, durante 5 días.El corte evaluativo se realizó cuando todos los pacientes tenían por lo menos 3 meses de intervenidos, 2 pacientes presentaron retardo en reepitelización conjuntiva durante las 2 primeras semanas de postoperatorio, que remitieron al final de este período. Dos pacientes presentaron recurrencia (10), teniendo estos las características de historia de más de una recidiva anterior, del grupo etáreo de25 a 34 años, además que fueron intervenido 1 año después de su ultima recurrencia. Se concluyó que el uso de Mitomicina C como porfilaxis en prevenir la recurrencia, es un método seguro y eficaz; y que los pacientes mas jovenes (grupo de 15 a 34 años), del sexo masculino, y con historia de más de recurrencia anterior, o recurrencia última de un año o menor, tienen mayor probalidad de enfrentar una nueva recidiva, aún con el uso de la profilaxis. Se recomendó preferir la técnica de escisión simple más la instalación postquirúrgica de Mitomicina C, a fin de evitar las recurrencias...

[Respiratory complications of the vinorelbine-mitomycin combination]. / Complications respiratoires de l'association vinorelbine-mitomycine.

The respiratory toxicity of vinca alkaloids only appears when they are associated with mitomycin. Few reports have been noted with vinorelbine, the last molecule of this class. We report 4 cases of acute dyspnea induced by the association mitomycin-vinorelbin, The 4 patients were treated for lung cancer. At the end of the injection of vinorelbin appeared an acute bronchospasm. In 3 cases, the symptoms disappeared with broncho-dilatators and corticoids. The fourth patient needed an additional respiratory support. After the acute syndrome, a chronic respiratory insufficiency developed in three patients. Two patients required continuous oxygenotherapy. The pulmonary toxicity of the mitomyin-vinca alkaloids association is characterized by an acute dyspnea. The dyspnea appears within 2 hours after the end of the administration of vinorelbine. The frequent existence of airflow obstruction in patients with lung cancer exposes to high risk of severes incidents. These treatments must be stopped at onset of the first pulmonary symptom. The association of mitomycin with vinorelbine (as for all vinca alkaloids) in chemotherapy protocols for treatment of non-small-cell lung cancer should not be indicated because there is an increase of the toxicity without increase of efficiency.

Mitomycin, ifosfamide and cisplatin in advanced non-small cell lung cancer.

BACKGROUND: Chemotherapy can be used to palliate the symptoms in patients with advanced non-small cell lung cancer. PATIENTS: Twenty-four chemo-naive patients with stage IIIB and IV non-small cell lung cancer were treated with the MIC regimen (mitomycin, ifosfamide and cisplatin). RESULTS: The overall response rate was 33% (partial response) and median duration of response was 7 months (range 5 to 10 months). At median follow-up of 26 months, the median survival was 8 months, and 1-year survival was 29%. Toxicities were tolerable. CONCLUSION: This appears to be a reasonable regimen for palliating advanced non-small cell lung cancer.

Effectiveness and complications of mitomycin C use during pediatric glaucoma surgery.

PURPOSE: To examine the safety of mitomycin C (MMC) use in pediatric glaucoma surgery. DESIGN: Retrospective interventional case series. PARTICIPANTS: One hundred eighty pediatric glaucoma patients younger than 7 years of age (254 eyes) who underwent glaucoma surgery and were followed for at least 1 year participated. INTERVENTIONS: Surgeries consisted of trabeculectomy or combined trabeculotomy-trabeculectomy with adjunctive use of MMC. MAIN OUTCOME MEASURES: Control of intraocular pressure (IOP) and occurrence of complications were measured. An IOP below 21 mmHg without any additional medical or surgical treatment was considered a success. RESULTS: Primary congenital glaucoma was present in 98% of the patients. Sixty percent had a trabeculectomy, and 40% had a trabeculotomy-trabeculectomy. The combined surgery was performed mostly in infants up to 1 year of age. Complications were cystic bleb (19), bleb leak (4), retinal detachment (3), flat anterior chamber (3), cataract (2), and endophthalmitis (1). Children younger than 2 years of age had fewer complications but higher failure rates. The combined procedure in infants up to 2 years of age was moderately more successful (57%) than trabeculectomy alone (39%). Minimal complications seen in this group were more likely related to young age than to the type of surgery. Complications increased with time after surgery, with most occurring 2 years or more after surgery. CONCLUSIONS: Success of MMC-augmented glaucoma filtering surgery increased with age, as did the complication rate. Serious complications were uncommon in the authors' group of pediatric patients up to now. However, complications related to bleb thinning increased with time after surgery, and additional problems can be anticipated with longer follow-up.

A phase II trial of four courses of preoperative chemotherapy in squamous or anaplastic carcinoma of the oesophagus.

We have reported the results of a previous Phase II trial of two courses of neoadjuvant mitomycin (6 mg/m2), ifosfamide (3 g/m2) and cisplatin (50 mg/m2) (MIC) in squamous or anaplastic carcinoma of the oesophagus. In this current study, we have investigated whether there was any clinical benefit in extending the preoperative treatment to four courses for patients who responded after two courses. Response was assessed by barium swallow, which was compared with previous barium swallows performed prior to any treatment and after the second course of MIC. Of an initial 43 patients, 27 (63%) were assessed as responders after two courses of MIC. Twenty of these 27 patients were entered into the study with a view to receiving two further courses of MIC prior to surgery. Seventeen completed four courses. Five patients were complete responders after two courses and remained complete responders after four courses. Twelve patients were partial responders after two courses; six of these became complete responders after four courses, five remained partial responders, and one showed progression. Haematological toxicity and alopecia were increased after extending the number of courses beyond two. On pathological assessment, three patients with a complete response after four courses, and one with a complete response after three courses, had microscopic clearance of tumour. Extension beyond two courses of neoadjuvant MIC gives an improvement in response, as judged by barium assessment, but increases toxicity, cost of treatment and delay before surgery. Although the numbers are small, the results suggest that a worthwhile improvement in the radiological response of squamous or anaplastic oesophageal tumours may be gained by proceeding beyond two courses of MIC. A randomized trial, with larger numbers of patients, is needed to show whether there is any improvement in radiological and pathological response rates and in survival to be gained by the extension of treatment beyond two courses.

A phase II trial of preoperative mitomycin, cisplatin and 5-fluorouracil in adenocarcinoma of the oesophagus.

The effect of neoadjuvant chemotherapy in patients with apparently operable adenocarcinoma of the oesophagus has been investigated. Two courses of mitomycin, cisplatin and 5-fluorouracil (MCF) were given, followed by a radiological evaluation of response. Twenty-two of 25 patients completed both courses. Two showed a complete response and 12 a partial response. There was a pathological complete response of the primary tumour in only one patient (although there was residual secondary tumour in a local lymph node). The main toxicity was myelosuppression, with 9/22 patients having the second chemotherapy course delayed. There were three sudden deaths, one due to a pulmonary embolus and two due to complications of infections. Twenty-one patients underwent surgical exploration; there were 18 resections. Although the radiological response rate of MCF (14/25; 56%; 95% CI 37-75) appeared promising, there were no pathological complete responders. Further Phase II trials are needed to identify more efficacious agents and regimens that will yield a pathological response rate of at least 10%, before proceeding to randomized trials of neoadjuvant chemotherapy for adenocarcinoma of the oesophagus.

Docetaxel vs mitomycin plus vinblastine in anthracycline-resistant metastatic breast cancer.

This nonblinded, multicenter, randomized phase III study compares the median time to progression (primary endpoint), response rate, and quality of life, safety, and survival of docetaxel (Taxotere) vs mitomycin (Mutamycin) plus vinblastine (Velban) in patients with metastatic breast cancer in whom previous anthracycline-containing chemotherapy has failed. Patients were randomized to receive an intravenous infusion of either 100 mg/m2 of docetaxel for 1 hour every 3 weeks, or 12 mg/m2 of mitomycin every 6 weeks plus 6 mg/m2 of vinblastine every 3 weeks. This preliminary analysis presents data on 200 patients among 392 patients recruited. Median time to progression was longer in the group treated with docetaxel compared with the mitomycin/vinblastine group (17 vs 9 weeks). The overall response rates were higher with docetaxel (28% vs 13%, respectively), and fewer patients in the docetaxel group had progressive disease as their best overall response (29% vs 48%). As expected, thrombocytopenia was more common in the mitomycin/vinblastine group, and neutropenia occurred more frequently in the docetaxel group. Severe fluid retention in the docetaxel group (8.7%) resulted in treatment discontinuation in 5 patients (5%). Severe thrombocytopenia (12%) and constipation (6%) led to treatment discontinuation in 7 and 3 patients, respectively, in the mitomycin/vinblastine group. Based on this preliminary analysis, docetaxel appears to be equally as safe as and more active than mitomycin/ vinblastine in patients with metastatic breast cancer in whom previous anthracycline-containing chemotherapy has failed. These results are subject to cautious interpretation because this analysis was conducted on the first 200 patients who finished the study treatments, and these preliminary results may underestimate response and overstate treatment discontinuation rates. Thus, the final analysis on the entire patient population is necessary to confirm these preliminary findings.