Extended-schedule oral etoposide in selected neoplasms and overview of administration and scheduling issues.

Extended schedules of oral etoposide have been evaluated in many types of advanced cancer. In addition to their use in the common solid tumours, extended schedules have been employed in Kaposi's sarcoma (both AIDS-related and endemic types), medulloblastoma, glioma, and hepatocellular carcinoma. Single agent activity was demonstrated in all of these tumour subtypes.

Oral etoposide in lymphoma.

Etoposide is one of the most active agents for the therapy of lymphomas. Oral etoposide has proven to be active in and clearly beneficial for patients with previously treated lymphomas. The optimal dose and schedule of oral etoposide for use in combination chemotherapy are still uncertain, but low daily doses (50 to 100 mg) for 10 to 14 days may be near optimal.

Phase II trial evaluating triplet chemotherapy using gemcitabine, paclitaxel, and carboplatin in the treatment of patients with advanced non-small cell lung cancer.

The purpose of this study was to evaluate the combination of gemcitabine, paclitaxel, and carboplatin in patients with advanced non-small cell lung cancer. Previously untreated patients with stage IIIB or IV non-small cell lung cancer were enrolled into this trial. Sixty-nine patients from the phase II portion and eight patients from the phase I portion were treated with gemcitabine 1,000 mg/m2 intravenously on days I and 8, paclitaxel 200 mg/m2 as a 1-hour infusion on day 1, and carboplatin at an area under the curve of 5.

Overexpression of Her-2 in patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site.

Purpose: To determine the frequency of Her-2 overexpression in patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site.

Patients And Methods: Tumor specimens from 100 patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma were stained for the Her-2 protein using the Dako immunohistochemical method. Clinical and pathologic characteristics of patients with and without Her-2 overexpression were compared.

The evolving role of oral topotecan.

Pharmacokinetic characteristics, efficacy, and safety of oral topotecan, a topoisomerase-I inhibitor, were evaluated in phase I and phase II clinical trials. Results of the pharmacokinetic analyses showed that orally administered topotecan has a lower peak plasma concentration (Cmax) and longer mean residence time than intravenously administered drug. Preliminary data suggest that the oral formulation has efficacy similar to that of the intravenous (IV) formulation in patients with recurrent or refractory ovarian and small-cell lung cancer.

Docetaxel (Taxotere) administered in weekly schedules.

The administration of a weekly low-dose taxane markedly reduces the severity of myelosuppression compared with a once-every-3-week schedule and allows the dose intensity (mg/m2/wk) of treatment to be increased. The dose-limiting toxicity observed in a weekly phase I trial was fatigue/asthenia. The maximum tolerated dose of a weekly docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) phase I study was 43 mg/m2; 36 mg/m2 was recommended for further study.

Single-agent docetaxel (Taxotere) in randomized phase III trials.

Until recently, there has been no standard treatment for patients with metastatic breast cancer who have failed an anthracycline-containing regimen, and no definitive phase III trials had been conducted in this setting. The results of three randomized phase III clinical trials of single-agent docetaxel (Taxotere, Rhône-Poulenc Rorer, Collegeville, PA) 100 mg/m2 every 3 weeks in comparison to combination chemotherapy regimens in patients with metastatic breast cancer pretreated with an anthracycline-based chemotherapy regimen are reviewed and reported. An overall response rate of between 30% and 42% was reported for single-agent docetaxel, which was higher in comparison to response rates attained with the combination chemotherapy regimens in all three trials.

Topotecan: Incorporating It Into the Treatment of Solid Tumors.

This issue of The Oncologist provides the reader with two useful reviews of the new chemotherapeutic agent topotecan, one of a class of topoisomerase I inhibitors that is being studied and incorporated into the treatment of various malignancies. Topotecan was approved for the treatment of refractory ovarian cancer in 1996, and has shown promising activity against a variety of solid tumors, as well as hematologic malignancies. One paper discusses clinical guidelines for managing topotecan-related hematologic toxicities, and centers on data derived from ovarian cancer studies.

Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer: preliminary results of a Minnie Pearl Cancer Research Network phase II trial.

Purpose: To evaluate the feasibility, toxicity, and therapeutic efficacy of 1-hour paclitaxel, carboplatin, continuous low-dose infusional 5-fluorouracil, and concurrent radiation therapy administered preoperatively in patients with localized esophageal cancer.

Patient And Methods: Forty-nine patients with localized esophageal cancer, of either squamous cell carcinoma or adenocarcinoma histology, were enrolled into this phase II trial. All patients were candidates for surgical resection and received the following neoadjuvant therapy: paclitaxel, 200 mg/m2, 1 hour IV on days 1 and 22; carboplatin, AUC 6.

Mitoxantrone, 5-fluorouracil and high-dose leucovorin (NFL) in the treatment of metastatic breast cancer: randomized comparison to cyclophosphamide, methotrexate and 5-fluorouracil (CMF) and attempts to improve efficacy by adding paclitaxel.

The combination of mitoxantrone (12 mg/m2 i.v., day 1) 5-fluorouracil (350 mg/m2 i.

Paclitaxel, carboplatin, and long-term continuous 5-fluorouracil infusion in the treatment of upper aerodigestive malignancies: preliminary results of phase II trial.

We evaluated the efficacy and toxicity of a novel chemotherapy regimen that included paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), carboplatin, and long-term, continuous-infusion 5-fluorouracil in the treatment of cancers of the upper aerodigestive tract. In the preoperative treatment of patients with localized esophageal cancer, we administered this regimen concurrently with radiation therapy. Thirty-eight patients with biopsy-proven cancers of the head and neck or esophagus entered this trial between January 1996 and November 1996.

Paclitaxel, carboplatin, and extended-schedule etoposide in the treatment of small-cell lung cancer: comparison of sequential phase II trials using different dose-intensities.

Purpose: In two sequential phase II studies, we evaluate the feasibility and efficacy of adding paclitaxel to a standard platinum/etoposide regimen in the first-line treatment of small-cell lung cancer.

Patients And Methods: One hundred seventeen patients with small-cell lung cancer were treated between June 1993 and July 1996. The first 38 patients received a lower-dose regimen: paclitaxel 135 mg/m2 by 1-hour infusion, carboplatin at an area under the concentration-time curve (AUC) of 5.

Chemotherapy in the treatment of non-small cell lung cancer.

Non-small cell cancers of the lung include squamous cell carcinoma, adenocarcinoma and large cell carcinoma. These tumors have traditionally been considered to be quite resistant to both chemotherapy and radiation therapy. Although surgery has offered the best chance for cure, the tumor has usually spread too far for effective surgery by the time it is discovered.

Mitoxantrone, 5-fluorouracil, and high dose leucovorin (NFL) versus intravenous cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in first-line chemotherapy for patients with metastatic breast carcinoma: a randomized phase II trial.

Background: Previous Phase II studies using the combination of mitoxantrone, 5-fluorouracil, and high dose leucovorin (NFL) in the treatment of metastatic breast carcinoma have shown this regimen to be active and well tolerated. In this randomized Phase II study, the authors compared the NFL regimen with a standard CMF regimen in the first-line therapy of patients with metastatic breast carcinoma.

Methods: One hundred twenty-eight women receiving their first chemotherapy for metastatic breast carcinoma were entered into this randomized study.

Phase I study of high dose etoposide phosphatase with filgrastim (G-CSF) in the treatment of advanced refractory malignancies.

Purpose: To define the maximum tolerated dose of etoposide phosphate when used with G-CSF in the treatment of patients with refractory malignancies.

Patients And Methods: Eleven patients with advanced cancer refractory to standard therapy were treated with etoposide phosphate given over 1-2 hours on three consecutive days. The first cohort of patients received a total dose of 1596 mg/m2 (equivalent to etoposide 1400 mg/m2); doses were escalated in subsequent patient cohorts.

The tumor conference: an integral component of the oncology program.

This periodic meeting of individuals with oncologic expertise represents the best that modern medicine can be: a true multidisciplinary approach to patient care. Nowhere else in healthcare will you find a better example of combining different expertise for the express purpose of improving the delivery of care for an individual patient.

One-hour paclitaxel in the treatment of non-small cell lung cancer.

This review describes studies with two paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)-containing treatments for non-small cell lung cancer (NSCLC). In an ongoing study, 100 patients with previously untreated stage IIIB or IV NSCLC received combination therapy comprised of paclitaxel 225 mg/m2 via 1-hour infusion and carboplatin, dosed to an area under the concentration-time curve of 6.0.

Paclitaxel in lung cancer: 1-hour infusions given alone or in combination chemotherapy.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 1-hour infusion potentially offers its recipients reduced toxicity, demonstrated efficacy, and greater ease of administration. To confirm this hypothesis, we undertook a phase I/II study of 1-hour, single-agent paclitaxel in 164 patients' refractory malignancies; 59 patients with recurrent or stage IV non-small cell lung cancer (NSCLC) participated in the study. Our objective was to compare two paclitaxel doses (135 and 200 mg/m2) and two 1-hour infusion schedules (1 hour in 1 day, or 1 hour each day for 3 days, divided dose).

Paclitaxel administered by a 1-hour infusion: A phase I-II trial comparing two schedules.

Purpose: Paclitaxel is currently administered by prolonged intravenous infusion primarily because of severe hypersensitivity reactions that occurred with rapid infusions during early clinical trails. This phase I-II study evaluates the feasibility of 1-hour paclitaxel administration and compares the toxicity and efficacy of two different 1-hour infusion schedules.

Patients And Methods: One hundred sixty-four patients with advanced, refractory cancer were randomized to receive one of two paclitaxel schedules: a 1-hour infusion or a 3-day, divided dose schedule, each daily dose administered by 1-hour infusion.