Advanced bronchioloalveolar carcinoma: a phase II trial of paclitaxel by 96-hour infusion (SWOG 9714): a Southwest Oncology Group study.

BACKGROUND: There are no published prospective trials of chemotherapy for advanced bronchioloalveolar carcinoma (BAC), a subtype of non-small-cell lung cancer for which there is no current standard therapy. This phase II study assesses the efficacy and toxicity of 96-h paclitaxel in chemotherapy-naive patients with advanced BAC. PATIENTS AND METHODS: Patients with histologically confirmed stage IIIB (with pleural effusion) or stage IV BAC were eligible. Treatment consisted of paclitaxel 35 mg/m2/24 h continuously infused over 96 h (days 1-4) every 21 days for up to six courses. RESULTS: A total of 58 eligible patients were enrolled. The objective response rate was 14% (all partial responses, 9% confirmed); 40% of patients demonstrated stable disease. The median progression-free and overall survivals were 5 and 12 months, respectively. Grade 3 or greater toxicities included neutropenia/granulocytopenia (43%), febrile neutropenia (12%), infection (22%), and stomatitis/pharyngitis (10%); there were five treatment-related deaths. CONCLUSIONS: S9714 represents the first prospective multi-institutional cooperative group trial focusing on treatment outcomes in BAC. Studies targeting this population are feasible, and while first-line paclitaxel administered as a prolonged infusion is active in this setting, toxicities limits the utility of this regimen. S9714 serves as a historical control for BAC patients against which future therapeutic approaches can be compared.

Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer: a Southwest Oncology Group study.

BACKGROUND: Eniluracil is a potent, irreversible inactivator of dihydropyrimidine dehydrogenase, the major catabolic enzyme for 5-fluorouracil (5-FU). Pretreatment with eniluracil significantly increases plasma half-life, plasma concentration and oral bioavailability of 5-FU. This multicenter phase II trial was designed to estimate the 6-month survival rate in patients with metastatic adenocarcinoma of the pancreas treated with 5-FU and eniluracil. PATIENTS AND METHODS: One hundred and sixteen patients (61 with no prior chemotherapy and 55 with prior chemotherapy) were registered for treatment with eniluracil 50 mg (total dose) p.o. on days 1-7 and 5-FU 20 mg/m(2)/day p.o. on days 2-6 of a 28-day treatment cycle. RESULTS: In 106 patients evaluable for survival, the 6-month survival rate was 34% [95% confidence interval (CI) 22% to 47%, median survival 3.6 months] for patients who had not been treated previously with chemotherapy and 29% (95% CI 16% to 42%, median survival 3.4 months) for those who had received prior chemotherapy. For those patients with measurable disease, the confirmed response rates were 8% and 2%, respectively. The most common grade 3-4 toxicities were neutropenia (29% of patients) and diarrhea (12% of patients). Overall, 69% of patients experienced a grade 3 or worse adverse event during treatment. CONCLUSIONS: These results suggest that the combination of a 7-day course of eniluracil and a 5-day course of oral 5-FU has limited activity in patients with advanced pancreatic cancer, and is associated with a high frequency of clinically significant adverse events.

Evaluation of gemcitabine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Southwest Oncology Group phase II study.

A phase II trial of gemcitabine (Gemzar), a nucleoside analogue with broad activity in solid tumors, was performed in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. A total of 26 eligible patients were registered to receive a dose of 1250 mg/m2 weekly for 3 weeks, followed by a 1 week rest. Toxicity was evaluable in 26 patients. Nausea and vomiting occured in 11 and 6 patients, repectively. Grade 3 or 4 hematologic toxicities were infrequent. Two patients developed neutropenic infections. One patient developed fatal liver failure which was thought due to progressive liver metastases or infection 14 days after a single dose of gemcitabine. There were no objective treatment responses (95% CI 0-13%), with a median survival of 6 months in this highly resistant disease population. Gemcitabine is not considered active enough as monotherapy for further evaluation in this disease population.

Advances in diagnosis and therapies for breast cancer.

Major achievements in the field of breast cancer research have occurred in the last year. Improved treatment options with reduced toxicities, better methods of diagnosing disease at a low stage and determining women who are at genetic risk, and the prospect of breast cancer prevention will hopefully translate into further reductions in breast cancer incidence and mortality.

Carmustine, Ara C, cyclophosphamide and etoposide with autologous bone marrow transplantation in relapsed or refractory lymphoma: a dose-finding study.

The purpose of this study was to define the dose-limiting non-hematologic toxicity of carmustine, Ara C, cyclophosphamide and etoposide (BACE). Between October 1986 and March 1990, 37 patients with relapsed or refractory lymphoma received escalating doses of combination chemotherapy followed by autologous bone marrow transplant (ABMT). Twenty patients with Hodgkin's disease (HD) and 17 patients with intermediate or high grade non-Hodgkin's lymphoma (NHL) initially received conventional-dose therapy with either a 7 week course of modified MACOP-B or a single dose of cyclophosphamide (CY) at 2 g/m2 depending on prior therapy and response. Regardless of response, patients then received escalating doses of BACE, toxicity permitting. Ten patients obtained complete responses (CR) and 12 patients were partial responders (PR), CR+PR (75%) with modified MACOP-B and 7 (64%) patients obtained PR with CY. The maximum-tolerated dose (MTD) for BACE was determined to be carmustine 700 mg/m2, Ara C 1500 mg/m2, CY 150 mg/kg and etoposide 1500 mg/m2. When Ara C was escalated from 1500 mg/m2 to 3000 mg/m2 holding the other drugs at the prior doses, the next two patients died secondary to diffuse alveolar damage. Overall and event-free survivals are identical with 14 of 37 patients (38%) alive with a median follow-up of 61 months (range 38-79 months). Ten patients were treated at the MTD, none of whom died a toxic death and 3 (30%) are alive with a median follow-up of 42 months (range 38-52 months). We defined the MTD and BACE showing pulmonary toxicity to be the dose-limiting non-hematologic toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Enlargement of mediastinal masses on simulation films: a radiotherapeutic problem in the management of patients with Hodgkin's disease.

The size of the mediastinal mass on standard posterior-anterior chest radiograph in stage I and stage II Hodgkin's disease has both prognostic and therapeutic importance. But the actual treatment is based on the anterior-posterior supine simulation film. Problems arise when the prognosis (whether all the disease can be effectively contained in an irradiation port) and toxicity (more lung and heart irradiated or chemotherapy required) are changed when the mass is markedly enlarged on the radiation simulation films. Differences in the direction of the X-ray beam, distance from the subject, and patient position are shown to increase artificially the size of a mediastinal mass on simulation films. The staging and therapeutic implications are discussed.

The clinical significance of unconventional orchiectomy approaches in testicular cancer: a report from the Testicular Cancer Intergroup Study.

Despite the clear indications for an inguinal approach, reports indicate that up to 53 per cent of all testicular tumors are diagnosed or initially treated in a manner inconsistent with the classical radical orchiectomy. Of 462 evaluable patients from the Testicular Cancer Intergroup Study 47 (10.2 per cent) had undergone a nonclassical orchiectomy as the initial surgical management. This group was analyzed separately to determine the prognostic significance of needle aspiration, open biopsy, a scrotal approach and tumor contamination. Within this group of patients, those who received no adjuvant chemotherapy exhibited no increase in local or distant recurrence. While the recurrence rate similarly was not adversely affected by even gross tumor contamination, this subset underwent significantly more aggressive local surgical salvage (p less than 0.01), with scrotectomy procedures found to be of probable therapeutic value. While not to be condoned, we conclude that deviations from the classical orchiectomy, when followed by appropriate surgical management and close observation, can be of little clinical impact.

Procarbazine hypersensitivity manifested as a fixed drug eruption.

A case of a previously unrecognized form of hypersensitivity to procarbazine characterized by a nonpigmented fixed drug eruption is reported. Despite skin testing, association of the skin lesion to procarbazine could be determined only by drug rechallenge. Various aspects of procarbazine hypersensitivity reactions as well as the pathogenesis and importance of the fixed drug eruption are discussed.