Phase II of doxorubicin/taxol in metastatic breast cancer. Argentine Multicenter Taxol Group.

PURPOSE: To assess the response rate, survival, and toxicity of Taxol (paclitaxel) as 1-h infusion plus doxorubicin as first-line treatment for patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Seventy-six patients with untreated MBC were recruited. All of them had measurable disease and were evaluable for toxicity. Fifty-five percent of the patients had visceral involvement. The dose of doxorubicin was fixed at 50 mg/m2 as a short intravenous infusion, followed by 200 mg/m2 of Taxol as a 1-h intravenous infusion. Doxorubicin was administered during the first seven cycles, continuing with Taxol only up to a maximum of ten cycles. RESULTS: Neutropenia was the most important toxicity: 30% grade 3 and 18% grade 4. Only 2 patients showed a decrease in the left ventricular ejection fraction (LVEF) which caused discontinuing the treatment. No clinical congestive heart failure (CHF) was observed. Seventy-four patients were eligible for response evaluation: 10 (14%) achieved complete response (CR) and 46 (62%) achieved partial response (PR). The mean duration of response was 13.47+/-1.35 months (95% confidence interval (CI): 10.82; 16.12) and the mean survival was 21.50+/-1.42 months (95% CI: 18.72; 24.29). CONCLUSION: The overall response (OR) rate was 76%. No CHF was assessed and 2 patients stopped treatment due to LVEF decrease. Although doxorubicin 50 mg/m2 followed by Taxol 200 mg/m2 in 1-h intravenous infusion presents a toxicity profile which demands a close follow-up, it represents a convenient outpatient schedule with similar activity rate compared to longer Taxol infusions.

Paclitaxel in platinum-resistant ovarian cancer patients. Argentine Multicenter Taxol Group.

Paclitaxel (Taxol; Bristol-Myers Squibb Company; Princeton, NJ) is an antineoplastic agent that inhibits microtubular function and has shown efficacy in several solid tumors, mainly ovarian tumors, in which 20% to 40% response rates in previously treated patients were observed. We conducted a study to assess survival, response rate, and toxicity associated with paclitaxel treatment in patients with advanced ovarian cancer resistant to platinum therapy. Between September 1994 and November 1996, 38 patients were admitted for study and 37 were evaluable. All had disease progression or relapse within 1 year of receiving platinum-containing first-line chemotherapy. Mean age was 59 years (range, 30 to 75 years), all had bulky disease, and 18 showed increased carbohydrate antigen-125 at admission. They were treated every 3 weeks with paclitaxel 175 mg/m2 as a 3-hour infusion, preceded by standard premedication. Response rate was 51.3%, with a median response duration of 10.0 months and a median survival rate of 16.8 months. Mild to moderate hematologic toxicity was observed with only one episode of grade 4 neutropenia, without fever. Gastrointestinal toxicity was moderate and peripheral neuropathy was mild, except for two patients who had concomitant pathologies or previous treatment, which might have caused some neuropathy. We concluded that paclitaxel given as a 3-hour infusion was easily administered for ambulatory treatment, with mild to moderate toxicity and promising results based on rate and duration of response as well as survival.

Treatment of non-small cell lung cancer with ifosfamide (IFO)+ 4'-epiadriamycin (EPI)+platinum vs. IFO+EPI: a GETLAC Study. Grupo de Estudio y Tratamiento Latinoamericano del Cáncer Study.

203 patients with inoperable non-small cell lung cancer (NSCLC) were randomized to receive ifosfamide (IFO) 2.5 g/m2 days 1-2 + epirubicin (EPI) 70 mg/m2 day 1 with cisplatin (DDP) 70 mg/m2 day 1 (arm IEP), or without cisplatin (arm IE). For uroprophylaxis, mesna i.v. 20% of IFO dose, hour 0 and 3, and oral, 40% of IFO dose, hour 6 and 9, days 1-2 was given. Cycles were repeated every 28 days. Four cycles were required for evaluation purposes. After completion of chemotherapy, external beam irradiation 40 Gy was given over 4 weeks for stage III B responders. Most of the patients with stable disease, partial response or complete response (CR) received 6 cycles. The median follow-up of the trial is 30 months. There were no differences in overall response rates: arm IEP: 52% (2% CR); arm IE: 51% (13.5% CR). Median time to progression was 6 months (arm IEP) and 4 months (arm IE) (p = 0.4844). Toxicity ranged from mild to moderate. Nephrotoxicity was not seen; only 6 patients had neurotoxic side effects of short duration. Median survival according to treatment was 12 months for IEP arm (12% at 2 years) and 10 months for IE arm (21% at 2 years). IFO/mesna+EPI or IFO/mesna, EPI plus DDP appeared to be an active and well tolerated combination for the treatment of NSCLC, with a good survival time.

Tratamiento sistémico del cáncer avanzado de ovario con interferón ß y quimioterapia / Systematic treatment of the advanced ovarian cancer with ß interferon and chemotherapy

El cáncer de ovario es una de las causas de muerte más común dentro de las neoplasias ginecológicas, por lo que los tratamientos de rescate son de considerable interés; así, se desarrollaron tratamientos con esquemas que contienen platino, de elección en estadios avanzados. En nuestra presente experiencia encontramos que la combinación carboplatino-ifosfamida, mesna, 4 epirrubicina y el interferón ß es una alternativa efectiva y tolerable, pues 4 de las pacientes obtuvieron respuesta completa luego de la cirugía de rescate. Para obtener conclusiones definitivas, es necesario un mayor número de pacientes y tiempo de observación.

Tratamiento sistémico del cáncer avanzado de ovario con interferón ß y quimioterapia / Systematic treatment of the advanced ovarian cancer with ß interferon and chemotherapy

El cáncer de ovario es una de las causas de muerte más común dentro de las neoplasias ginecológicas, por lo que los tratamientos de rescate son de considerable interés; así, se desarrollaron tratamientos con esquemas que contienen platino, de elección en estadios avanzados. En nuestra presente experiencia encontramos que la combinación carboplatino-ifosfamida, mesna, 4 epirrubicina y el interferón ß es una alternativa efectiva y tolerable, pues 4 de las pacientes obtuvieron respuesta completa luego de la cirugía de rescate. Para obtener conclusiones definitivas, es necesario un mayor número de pacientes y tiempo de observación. (AU)

Combined polychemotherapy in the treatment of primitive lung cancer of the "non-oat cell" type.

Forty-one patients (30 males, 11 females; mean age 49.7 years) with diagnosis of the "non-oat cell" type of lung cancer were studied. All patients were included in a randomized treatment design (regimens A and B) and completed six full cycles of polychemotherapy. Only 28 of the 41 patients proved evaluable. The performance status was 0-2 in 20 subjects (71.4%) and 3-4 in 8 (28.6%). The total number of patients achieving partial and complete responses was 20 (71.4%), of whom 14 (70%) received CDDP and the other 6 DDR. A progression of the disease was seen in 8 patients (28.6%), of whom 5 (62.5%) received DDR and the other 3 (37.5%) CDDP. An increase in body weight (3-8 kg) was observed in 15 patients (53.6%). Twenty-four of the 28 patients (85.7%) had a subjective feeling of well-being throughout the 6 cycles of chemotherapy. Nausea and vomiting and alopecia were the most frequent side-effects. The most important complications were paralytic ileus in 2 cases and a darkish manifestation in forearm and hand tissue due to vinblastine extravasation in another 2 cases. Haematological toxicity was found to be acceptable: leucopenia (less than 3.000) in 30 patients (73.2%); and thrombocytopenia (less than 100.000) in 12 patients (29.2%), which proved reversible. Some modalities relative to treatment schemes and the incorporation of additional agents are discussed.