A phase II study in advanced breast cancer: ZD1694 ('Tomudex') a novel direct and specific thymidylate synthase inhibitor.

ZD1694 ('Tomudex'), a novel, direct and specific thymidylate synthase (TS) inhibitor, was developed in a collaborative research programme between Zeneca Pharmaceuticals and the Institute of Cancer Research (UK) and entered clinical trials in 1991; phase II studies began in 1992, using 3.0 mg m-2 every 3 weeks as a short 15 min infusion. Forty-six patients entered a phase II study of ZD1694 in advanced breast cancer.

Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer.

Purpose And Methods: The objective of this multicenter study was to compare the therapeutic index of two different doses of paclitaxel given as a 3-hour infusion in patients with metastatic breast cancer (MBC), who had failed to respond to previous chemotherapy. A total of 471 patients with MBC were randomized to receive intravenous paclitaxel at a dose of 175 or 135 mg/m2 every 3 weeks.

Results: Better treatment results were achieved with high-dose (HD) versus low-dose (LD) paclitaxel: overall response rate, 29% versus 22% (P = .

Phase I study of paclitaxel and epirubicin in patients with metastatic breast cancer: a preliminary report on safety.

Attempting to develop a new active, convenient regimen, we initiated a phase I study of paclitaxel (Taxol; Bristol-Myers squibb Company, Princeton, NJ) combined with epirubicin (Farmitalia Carlo Erba, Milan, Italy) in patients with metastatic breast cancer. In addition to standard eligibility criteria, patients with chemotherapy-naive metastasis and at least one measurable lesion had to have left ventricular ejection fractions of at least 50%; the metastatic relapse had to have occurred more than 6 months after adjuvant treatment. Anthracycline-pretreated patients could not have received cumulative doses of more than 300 mg/m2 doxorubicin, 450 mg/m2 epirubicin, or 70 mg/m2 mitoxantrone.

Pattern of failure in patients with inflammatory breast cancer treated by alternating radiotherapy and chemotherapy.

Background: Patients with inflammatory breast cancer have a high risk of developing a local recurrence and/or distant metastases. Treatment with combined chemotherapy and locoregional radiotherapy contributes to a decrease in both risks. This study presents treatment results and evaluates the pattern of failure when an alternating chemoradiotherapy schedule is used.

Hepatectomy for liver metastases from breast cancer.

Thirty-two selected patients underwent laparotomy in an attempt to resect one or more isolated liver metastases (LM) from breast cancer. Only 21 of them had hepatectomy and systematic lymph node picking of the hepatic pedicle. In six patients (19%), the discovery of diffuse metastatic disease contraindicated hepatectomy and in five patients (16%), the diagnosis of LM was erroneous, for lesions proved to be benign liver tumours.

High-dose ifosfamide: circumvention of resistance to standard-dose ifosfamide in advanced soft tissue sarcomas.

Purpose: The study was designed to assess the toxicity and activity of high-dose ifosfamide (HDI) administered by continuous infusion at a dose of 4 g/m2/d over 3 days every 4 weeks in adult patients with advanced soft tissue sarcomas (ASTS) pretreated with doxorubicin and/or a standard-dose ifosfamide (SDI)-containing regimen.

Patients And Methods: Between January 1991 and November 1993, 40 patients with progressive ASTS were entered onto the study. Twenty-eight patients had been pretreated with a multidrug regimen that contained SDI and were classified as follows: SDI-refractory (n = 21), SDI-resistant (n = 2), and indeterminate SDI-sensitive (n = 5).

[Mesenchymal breast sarcomas: general review].

Breast sarcomas are rare, representing 1% of all malignant breast tumors. A variety of histologies are found, the main ones being fibrosarcomas and malignant fibrohistiocytomas. Nodal involvement is rare and, as in other sarcomas, hematogenous spread of metastases is more usual.

Antiemetic treatment with oral granisetron in patients receiving moderately emetogenic chemotherapy: a dose-ranging study.

The antiemetic efficacy and tolerability of four different oral doses of granisetron (0.25, 0.5, 1, and 2 mg twice daily [BID]) were compared in a randomized, double-blind, parallel-group, multicenter study involving 930 patients with malignant disease receiving moderately emetogenic chemotherapy over a 7- or 14-day period.

Taxol (paclitaxel) in patients with metastatic breast carcinoma who have failed prior chemotherapy: interim results of a multinational study.

A multinational, randomized study has been conducted to compare the effectiveness and safety of two doses of Taxol (paclitaxel) (135 and 175 mg/m2, given as a 3-hour intravenous infusion every 3 weeks) in patients with metastatic breast carcinoma who had previously undergone treatment with one or two chemotherapeutic regimens. A total of 471 patients were enrolled in the study; the first 117 were included in an interim analysis that was planned in the protocol to identify any extreme efficacy differences between the treatment arms. Most (85%) of these initial patients were ambulatory with a performance status of 0 or 1 and multiple sites of disease.

Phase I/II trial of continuous infusion vinorelbine for advanced breast cancer.

Purpose: A phase I/II trial of vinorelbine (VRL) administered by continuous infusion (CIV) was conducted in advanced breast carcinoma (ABC) patients to determine the maximum-tolerated dose (MTD) and to evaluate the toxicity pattern and antitumor activity of this alternative administration schedule to the currently recommended weekly short intravenous (IV) administration.

Patients And Methods: Between February 1990 and July 1991, 64 consecutive, eligible patients with ABC were treated; 33 had received one or two previous palliative chemotherapy combinations and 31 had not received chemotherapy for metastatic disease. VRL was administered, after an initial IV bolus of 8 mg/m2 on day 1, by a 4-day CIV at five different 24-hour dose levels (DLs) to be repeated every 21 or 28 days: DL1, 5.

[Soft tissue sarcomas: general review].

Soft tissues sarcomas are an heterogeneous group of neoplasms. Their epidemiology is still poorly known. Great strides have been made in the genetic study over the last few years.

Association of c-erbB2-gene amplification with poor prognosis in non-inflammatory breast carcinomas but not in carcinomas of the inflammatory type.

It is now accepted that c-erbB2-gene amplification is correlated with poor clinical outcome for patients, mainly when axillary nodes are invaded. We have confirmed this result by multivariate analysis in 178 patients with non-inflammatory breast cancer followed up for a mean period of 6.8 years (SD, 1.

Phase II trial of vinorelbine/doxorubicin as first-line therapy of advanced breast cancer.

Purpose: The study investigated the therapeutic effects of a combination of Navelbine (vinorelbine or 5'noranhydrovinblastine; Pierre Fabre Médicament, Boulogne, France) and doxorubicin in women who had received no prior chemotherapy for locally advanced or metastatic breast cancer.

Patients And Methods: Ninety-seven patients with progressive and assessable advanced or metastatic breast cancer who had received no prior chemotherapy except in an adjuvant setting were entered onto the study. Eighty-nine patients were assessable for toxicity and response by World Health Organization (WHO) criteria; the other eight patients were excluded because they did not meet entry criteria or because of protocol violations.

Acute antiemetic efficacy and safety of dolasetron mesylate, a 5-HT3 antagonist, in cancer patients treated with cisplatin. European Dolasetron Study Group.

Dolasetron mesylate (MDL 73,147EF), a new serotonin receptor (5-HT3) antagonist was administered to 164 cancer patients naive or non-naive to chemotherapy, in single, rising doses of 10, 20, 30, 40, or 50 mg i.v. 15 minutes prior to an infusion of cisplatin.

Surgical resection of pulmonary metastases. Up to what number?

Specific results on the surgical resection of a large number of pulmonary metastases (PM) are currently unavailable, and the risk-benefit ratio of this aggressive approach may appear questionable. A systematic review of the records of 456 adult patients who underwent thoracic surgery for PM between 1979 and 1990 led to the identification of 44 patients who underwent at least one resection of eight or more PM (range eight to 110), of whom 33 (75%) had PM from osteogenic or soft tissue sarcoma. These 44 patients underwent a total of 77 operations, of which 47 (61%) were bilateral and nine (12%) incomplete resections.

[CA 15-3 and breast cancer].

The precise clinical value of CA 15-3 antigen has yet to be determined. With no role in screening for early breast cancer and, even if CA 15-3 seems to be correlated with bulky initial tumor burden, it appears to have no independent prognostic value. The clinical interest of CA 15-3 remains the early detection of the first recurrence.

[Treatment of advanced breast cancer in postmenopausal women with droloxifene: results of a double-blind phase II trial for dose determination].

To determine the optimal daily dose of a new antiestrogen, droloxifene, for the treatment of advanced breast cancer, we have conducted a multicenter, randomized, double blind trial. Postmenopausal women with advanced breast cancer, who could not benefit from loco regional therapy, with positive or unknown estrogen or progesterone receptors were entered in this study. Droloxifene was administered in a double blind randomized design, with daily dose of either 20 (group I), 40 (group II) or 100 mg (group III).

[Phase I trial of recombinant human granulocyte-macrophage colony stimulating factor. Results in patients with advanced tumors].

Fourteen patients with advanced solid tumors were included in a phase I trial of recombinant human E coli derived granulocyte-macrophage colony-stimulating factor (GM-CSF) given daily subcutaneously for 10 consecutive days. Dose levels were increased from 250 micrograms/m2 to 500, 750 and 1,000 micrograms/m2. Adverse effects were mainly fever, local irritation, lethargia, arthalgia.

Phase II study of elliptinium acetate salvage treatment of advanced breast cancer.

Elliptinium acetate (Celiptium) is an intercalating agent belonging to the ellipticine family. This agent has demonstrated clinical activity as salvage treatment in breast cancer using a weekly regimen. However, its clinical use was hampered by important toxicities such as xerostomia and immune-mediated haemolytic reactions due to development of anti-elliptinium IgM antibodies.