Outcomes of high-dose chemotherapy and autologous stem-cell transplantation in stage IIIB inflammatory breast cancer.

PURPOSE: To evaluate the disease-free survival (DFS) and overall survival (OS), prognostic factors, and treatment-related mortality of women with stage IIIB inflammatory breast cancer (IBC) treated with combined modality therapy (CMT) and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation. PATIENTS AND METHODS: Between 1989 and 1997, 47 consecutive patients with stage IIIB IBC were treated with CMT and HDCT and were the subject of this retrospective analysis. Chemotherapy was administered to all patients before and/or after definitive surgery. Neoadjuvant and adjuvant chemotherapy was administered to 33 and 34 patients, respectively, and 20 patients received both. All patients received HDCT with autologous stem-cell transplantation, and 41 patients received locoregional radiation therapy. Tamoxifen was prescribed to patients with estrogen receptor (ER)-positive cancer. RESULTS: The mean duration of follow-up from diagnosis was 30 months (range, 6 to 91 months) and from HDCT was 22 months (range, 0.5 to 82 months). At 30 months, the Kaplan-Meier estimates of DFS and OS from diagnosis were 57.7% and 59.1%, respectively. At 4 years, the Kaplan-Meier estimates of DFS and OS from diagnosis were 51.3% and 51.7%, respectively. In a multivariate analysis, the only factors associated with better survival were favorable response to neoadjuvant chemotherapy (P =.04) and receipt of tamoxifen (P =.06); however, the benefit of tamoxifen was only demonstrated in patients with ER-positive breast cancer. At last follow-up, 28 patients (59. 6%) were alive and disease-free. Seventeen patients (36.2%) developed recurrent breast cancer. Seventeen patients died: 15 from disease recurrence and two (4.2%) from treatment-related mortality due to HDCT. CONCLUSION: In this analysis, the early results of treatment with CMT and HDCT compare favorably with other series of patients with stage IIIB IBC treated with CMT alone. These outcomes must be confirmed with longer follow-up and controlled studies.

Efficacy and safety of oral granisetron versus oral prochlorperazine in preventing nausea and emesis in patients receiving moderately emetogenic chemotherapy.

PURPOSE: To compare the efficacy and safety of oral granisetron hydrochloride tablets with that of oral prochlorperazine sustained-release capsules in preventing nausea and emesis induced by moderately emetogenic chemotherapeutic agents. PATIENTS AND METHODS: In this multicenter, double-blind, randomized, parallel group study, oral granisetron and oral prochlorperazine were compared in 230 chemotherapy-naive, adult cancer patients who received moderately emetogenic chemotherapy. Patients were stratified by gender and randomized to receive either 1.0 mg oral granisetron HCI twice a day for 7 days, or 10 mg oral prochlorperazine sustained-release capsules twice a day for 7 days. The first dose was given 1 hour before initiation of chemotherapy and the second dose 12 hours after the first dose. Patients were evaluated for emetic episodes, extent of nausea, and adverse events for 7 days after the start of chemotherapy. Primary efficacy parameters were complete response (no emetic episodes, no greater than mild nausea, no antiemetic rescue) and total control (no emetic episodes, no nausea, no antiemetic rescue) in the 24 hours after the start of chemotherapy. RESULTS: Granisetron was significantly more effective than prochlorperazine in achieving a complete response (74% vs. 41%, respectively) and total control of nausea and vomiting (58% vs. 33%, respectively) at the 24-hour assessment. Complete response at 24 hours was significantly higher in the granisetron-treated patients than in prochlorperazine-treated patients. In women, granisetron showed a complete response rate of 69% versus 38% with prochlorperazine; in men, granisetron showed a complete response rate of 92% versus 61% with prochlorperazine. Both regimens were well tolerated, with headache (36% for granisetron, 29% for prochlorperazine) and constipation (31% for granisetron, 6% for prochlorperazine) the most common adverse events. CONCLUSIONS: : Oral granisetron 1 mg twice a day was significantly more effective than oral prochlorperazine sustained release capsules 10 mg twice a day in complete response and total control of nausea and vomiting at 24 hours after chemotherapy. Both agents were well tolerated.

3-Deazauridine (NSC 126849): an interesting modulator of biochemical response.

3-Deazauridine (NSC 126849) is a structural analog of uridine that inhibits the biosynthesis of Cytidine-5'-Triphosphate by competitive inhibition of Cytidine Triphosphate synthetase which is considered to be the primary mode of action of this nucleoside analog. Despite a paucity of clinical attention given to this drug as a single agent, it has generated much enthusiasm as a biological response modulator because of its synergistic effect with a number of antitumor agents including Cytosine Arabinoside, 5-aza-2'-deoxycytidine, 5-azacytidine, thymidine and D-galactosamine, although only the cytosine arabinoside/3-Deazauridine combination has been explored clinically. In this paper, the current status of the drug and future perspectives will be discussed.

Primary mediastinal germinomas in females: a case report and review of the literature.

Primary mediastinal germinomas in females are rare. Long-term survival ranges from 50 to 81%, depending on the initial extent of disease. Initial spread occurs intrathoracically and to regional nodes with late hematogenous dissemination. The roles of surgery, radiation therapy, and chemotherapy are discussed.

Phase I evaluation of chlorozotocin (NSC-178248): weekly schedule.

A phase I trial of chlorozotocin was completed for a weekly times four dose schedule repeated every 8 weeks. Thrombocytopenia was the acute dose limiting toxicity. Nausea and vomiting were moderate to severe and dose related. Two cases of possible drug related irreversible nephrotoxicity were seen. Transient elevations of serum creatinine and mild proteinuria were noted. Also, transient elevations in SGOT were observed. One patient with a carcinoid tumor had a 60% reduction in his 5HIAA level after one course of therapy. The recommended dose for phase II clinical studies of chlorozotocin is 40 mg/m2 IV weekly for four weeks, repeated every 8 weeks.