Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study.

PURPOSE: To compare the response rate, efficacy parameters, and toxicity profile of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5-FU/LV) as first-line treatment in patients with metastatic colorectal cancer. PATIENTS AND METHODS: We prospectively randomized 605 patients to treatment with oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection daily for 5 days in 4-week cycles. RESULTS: The overall objective tumor response rate among all randomized patients was significantly higher in the capecitabine group (24.8%) than in the 5-FU/LV group (15.5%; P =.005). In the capecitabine and 5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log-rank P =.72), median times to treatment failure were 4.1 and 3.1 months (P =.19), and median overall survival times were 12.5 and 13.3 months (P =.974), respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a significantly lower incidence (P <.0002) of diarrhea, stomatitis, nausea, and alopecia. Patients treated with capecitabine also displayed lower incidences of grade 3/4 stomatitis and grade 3/4 neutropenia (P <.0001) leading to significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P <.00001) and grade 3/4 hyperbilirubinemia were the only toxicities more frequently associated with capecitabine than with 5-FU/LV treatment. CONCLUSION: Oral capecitabine was more active than 5-FU/LV in the induction of objective tumor responses. Time to disease progression and survival were at least equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of tolerability.

Treatment of severe preeclampsia remote from term: a clinical dilemma.

UNLABELLED: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. Women with severe preeclampsia are usually delivered without delay. In recent years, a new approach in the treatment of women with severe preeclampsia remote from term has been advocated by several investigators worldwide. This approach advocates conservative management in a selected group of women with severe preeclampsia remote from term with the aim of improving perinatal outcome without compromising maternal safety. In most studies, patients who were candidates for conservative management had a blood pressure of more than 160/110, whereas in some studies, women with heavy proteinuria were also considered suitable. Only very few studies have supported conservative management in patients with signs and symptoms of HELLP syndrome. It is imperative to carefully balance maternal and fetal risks before choosing conservative management in severe preeclampsia remote from term. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to understand which patients are most likely to benefit from conservative management of severe preeclampsia remote from term, what the conservative management of severe preeclampsia remote from term entails, and what are the benefits of conservative management of preeclampsia remote form term.

The role of routine pelvic lymph node sampling in patients with stage I endometrial carcinoma: second thoughts.

BACKGROUND AND METHODS: The cases of 245 patients diagnosed during 1980-1989 with stage I endometrial carcinoma were retrospectively reviewed in order to assess the contribution of lymph node sampling (LNS) to both course of treatment and outcome. The 183 women treated by gyneco-oncologic surgeons had undergone the standard surgical procedure of total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO) and pelvic lymph node sampling (LNS). Sixty-two other women, treated by gynecologists, received only TAH and BSO. Of women who had received TAH+BSO+LNS, 105 (57.4%) were referred for adjuvant radiotherapy on the basis of one or any combination of high grade histology (G2 or G3), myometrial invasion to a depth of 50% or more and LNS positivity. Of the group who had not had LNS, 37 (59.7%) likewise received adjuvant radiotherapy but on the bases of histology and/or depth of invasion. RESULTS AND CONCLUSIONS: Recurrence and survival over a mean follow-up period of 7.5 years (range 5-15 years) showed no significant differences between the patients who underwent LNS and those who did not. Of 43 recurrences, six were among 'low risk' women (those with both minimal invasion and low grade histology), suggesting a special need among this group for the additional staging information which LNS may provide.

Nephrotoxicity of lomustine. A case report and literature review.

A patient is presented who developed nephrotoxicity after therapy with lomustine (CCNU) for astrocytoma of the brain. Only three other cases of lomustine nephrotoxicity have been reported, and all cases have been associated with cumulative drug doses of greater than 1,500 mg/m2. The clinical and pathologic features of lomustine nephrotoxicity are reviewed. It is recommended that cumulative doses of more than 1,200-1,4000 mg/m2 lomustine be avoided because of the risk of nephrotoxicity.

A Phase II study of Bruceantin (NSC-165, 563) in advanced malignant melanoma.

The Eastern Cooperative Oncology Group (ECOG) conducted a Phase II trial of Bruceantin in malignant melanoma. Twenty-two patients, thirteen without prior cytotoxic chemotherapy, were entered. All patients were evaluable for response and toxicity. Dose limiting toxicity was found to be hypotension during Bruceantin infusion. Other prominent side effects were nausea, vomiting, anorexia, fever, chills, and weakness. Only minor hematologic toxicity was encountered. Two partial responses, both in previously treated patients were observed (response rate -9%). Bruceantin has only limited activity against malignant melanoma and is unlikely to contribute to systemic therapy of this disease, either as a single agent or in combinations of cytotoxic drugs.

Phase II study of m-AMSA in advances malignant melanoma.

A phase II study of methanesulfonamide, N-(4-(9 acridinylamino)-3-methoxyphenyl)-(m-AMSA) was undertaken by the Eastern Cooperative Oncology Group. Thirty-five evaluable patients were studied, 18 of whom had had no prior therapy and eight of whom had been treated only one cytotoxic drug. Thirty-one of these patients were ECOG performance status 2 or better. The dose of m-AMSA employed in this study was 40 mg/M2 as an I.V. infusion over 20 minutes daily for 3 days, repeated every 3 weeks. Leukopenia was found to be dose-limiting; thrombocytopenia and anemia were also observed. Other prominent toxicities included anorexia, nausea, and vomiting. No cardiovascular toxicity was observed in this study, but none of the patients had received prior anthracycline therapy. Only one partial response of measurable disease was observed, all other patients had progressive disease on m-AMSA therapy. No significant clinical activity of m-AMSA against malignant melanoma was demonstrated in this very favorable group of patients.

Phase II trials of Baker's antifol, bleomycin, CCNU, streptozotocin, tilorone, and 5-fluorodeoxyuridine plus arabinosyl cytosine in metastatic breast cancer.

A total of 202 patients with advanced breast cancer were entered into two prospectively randomized Phase II trials conducted by the Eastern Cooperative Oncology Group, in an effort to identify promising agents and combinations for previously treated cases. Patients in Study 1 received bleomycin, CCNU, or streptozotocin and those in Study 2 received tilorone, Baker's antifol, or a combination of 5-fluorodeoxyuridine plus arabinosyl cytosine. Partial responses were seen only with bleomycin, Baker's antifol, and 5-fluorodeoxyuridine plus arabinosyl cytosine. The median times to treatment failure ranged from 3.6 weeks to 5.7 weeks, and the median survival times, from 8 weeks to 25 weeks for tilorone and bleomycin, respectively. Toxic reactions was primarily hematologic and gastrointestinal, but skin, neurologic, respiratory, and renal abnormalities were noted in some treatment arms. The treatment schedules outlined and the toxic effects noted provide background information that might prove useful in designing complex new chemotherapeutic programs, since there is pharmacological rationale for incorporating some of the agents tested into present standard combination chemotherapy regimens.

Phase I study of ethylbis(2,2-dimethyl-1-aziridinyl) phosphinate (AB-163).

Ethylbis(2,2-dimethyl-1-aziridinyl)phosphinate (AB-163) was used to treat 27 patients in a phase I trial. The limiting toxicity on a weekly schedule of IV administration involved nausea and vomiting associated with a variety of cholinergic side effects, including possible seizures. A starting dose of 300--400 mg/M2/week is suggested for a Phase II trial. One partial response in a patient with squamous-cell carcinoma of the cervix metastatic to the lungs was seen.