Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia.

Preliminary information has suggested that megestrol acetate leads to appetite stimulation and nonfluid weight gain in patients with breast cancer, other cancers, and AIDS. Pursuant to this, we developed a randomized, double-blind, placebo-controlled trial of megestrol acetate in patients with cancer-associated anorexia and cachexia. We randomly assigned 133 eligible patients to receive 800 mg of megestrol acetate per day or a placebo. Patients assigned to megestrol acetate more frequently reported improved appetite (P = .003) and food intake (P = .009) when compared with patients receiving the placebo. A weight gain of 15 lb or more over baseline was seen in 11 of 67 (16%) patients receiving megestrol acetate compared with one of 66 (2%) given the placebo (P = .003). Patients receiving megestrol acetate reported significantly less nausea (13% vs. 38%; P = .001) and emesis (8% vs. 25%, P = .009). No clinically or statistically significant toxic reactions were ascribed to megestrol acetate, with the exception of mild edema. This study convincingly demonstrated that megestrol acetate can stimulate appetite and food intake in patients with anorexia and cachexia associated with cancer, leading to significant weight gain in a proportion of such patients.

Comparison of cyclophosphamide, doxorubicin, and vincristine with an alternating regimen of methotrexate, etoposide, and cisplatin/cyclophosphamide, doxorubicin, and vincristine in the treatment of extensive-disease small-cell lung carcinoma: a Mid-Atlantic Oncology Program study.

An alternating regimen for the treatment of extensive-disease small-cell lung cancer (SCLC) was compared with standard treatment with cyclophosphamide, doxorubicin, and vincristine (CAV) in 170 patients. Overall severity of toxicity was similar in both arms, with four toxic deaths in each arm (4.7%). Response results were also similar, with 54% complete and partial responses with the standard regimen and 53% complete and partial responses with the alternating regimen. Median survival time was 6.9 months with the standard regimen and 9.2 months with the alternating regimen (P = .078). The 2-year survival rate was 1.2% for the standard regimen and 4.7% for the alternating regimen. Survival benefit for treatment with the alternating regimen reached statistical significance only in those subsets of patients with poorer prognosis (male sex, performance status 3, liver metastases, bone marrow metastases, and oat cell histologic subtype).

Hormonal palliation of chemoresistant ovarian cancer: three consecutive phase II trials of the Mid-Atlantic Oncology Program.

PURPOSE: To evaluate the efficacy of three hormonal manipulations in the palliation of chemoresistant ovarian cancer, and to analyze the results in the light of other clinical trials. PATIENTS AND METHODS: Three sequential phase II trials were performed in patients with refractory epithelial ovarian carcinoma, using high-dose megestrol acetate (800 mg/d for 30 days, then 400 mg/d), high-dose tamoxifen (80 mg/d for 30 days, then 40 mg/d), and aminoglutethimide (1 g/d plus tapering doses of hydrocortisone). Results were compared with those described in the world literature from trials of the same or similar agents. RESULTS: No responses were seen among 30 assessable patients treated with megestrol acetate, and most (but not all) similar trials have reported low response rates. Five responses (17%) were seen among 29 patients treated with tamoxifen. Two responses exceeded 5 years in duration. No responses were seen among 15 patients treated with aminoglutethimide. CONCLUSION: Antiestrogen therapy may offer the possibility of useful and, occasionally, long-term palliation of refractory epithelial ovarian carcinoma, with little toxicity. There may be a trend toward a dose-response effect, which represents a suitable topic for a future prospective trial.

Alleviation of cancer anorexia and cachexia: studies of the Mayo Clinic and the North Central Cancer Treatment Group.

Anorexia and cachexia are common clinical problems of many patients with advanced cancer. Approximately 20 years ago, a controlled, clinical study demonstrated that dexamethasone could stimulate appetites of patients with advanced gastrointestinal cancer without causing any apparent effect on patient weight or survival. More recently, two double-blind, placebo-controlled trials investigated cyproheptadine and megestrol acetate in patients with cancer anorexia/cachexia. The first of these studies suggested that cyproheptadine could mildly stimulate appetite without causing any discernible effect on patient weight. Megestrol acetate, on the other hand, can clearly cause an increase in patient-perceived appetite and food intake and can also lead to substantial nonfluid weight gain in a proportion of patients with cancer anorexia/cachexia. Ongoing studies have been designed to better study the appetite-enhancing effects of megestrol acetate. In addition, current studies are evaluating the effect of the drug hydrazine sulfate on the appetite and weight status of patients with advanced lung or colon cancer.

Breakthrough pain in cancer patients: characteristics, prevalence, and treatment.

"Breakthrough pain" is a common clinical term that has not been conclusively defined or described. Breakthrough pain is a transitory flare of pain experienced when baseline pain has been reduced to a mild or moderate level. Breakthrough pain may be characterized by its relationship to a fixed around-the-clock (ATC) opioid dose, rapid onset and short duration, precipitating events, predictability, pathophysiology (with nociceptive pain being most easily controlled), and etiology. The only prospective study of breakthrough pain conducted to date found a 63% prevalence of breakthrough pain in cancer patients referred to a pain service. Although prevalence figures from other studies vary widely, partly due to the populations chosen, all of the studies verify that breakthrough pain is a serious problem in cancer patients. In fact, several studies have listed incident pain, a subset of breakthrough pain, as a predictor of poor response to analgesic therapy. Breakthrough pain is currently managed with oral or parenteral breakthrough pain medications given in addition to the ATC analgesic regimen. The ATC dosage may also be increased until limited by side effects. Newer agents with a more rapid onset of analgesia and shorter duration of effect may help in the management of breakthrough pain.

Ethics and designs: laetrile trials as an example.

The National Cancer Institute instituted a search for cancer patients who have had objective benefit from Laetrile therapy. Cases have been solicited through a nationwide mailing to > 450,000 physicians and other health professionals, through publicity in the medical and lay press, and by contact with the pro-Laetrile groups. As a result, a retrospective analysis of the medical records of patients who volunteered their cases and who believed they had objective antitumor benefit from Laetrile therapy has been carried out. Similar criteria for response that are used for any National Cancer Institute-sponsored investigational agent were used to evaluate possible Laetrile antitumor activity. This analysis was not designed to determine a response rate to Laetrile. It is uncontrolled, only positive responders were solicited, and the total number of cases treated with Laetrile was not available. It is believed that if any objective benefit for Laetrila therapy exists, then at least hints of this should be made evident by this retrospective evaluation. Data collected were used to assist in deciding if clinical trials of Laetrile are warranted.

Health care providers' perspectives on breaking bad news to patients.

This article reports the results of an investigation designed to obtain descriptive information about what typically transpires in bad news transactions between patients and physicians. A sample of 115 health care providers who were attending a 1-day workshop on palliative care issues responded to questions regarding bad news transactions between physicians and patients. Results indicated that giving the news in person, giving the news in a private place, having patient support providers present, and using a warm and caring tone are highly typical of bad news transactions, whereas exploring patient emotional reactions, relying on touch, delivering the news at the patient's pace, and providing written information are less typical. Nurses and physicians diverged in the perceptions about what typically transpires, suggesting that studies focusing only on physician reports or recommendations may be misleading. These data also point to the need to obtain other views of bad news transactions, and they argue for research designed to assess the relation between actual patient-physician encounters and subsequent patient-related outcomes.

Plasma concentrations following single doses of morphine sulfate in oral solution and rectal suppository.

Plasma concentrations of morphine and morphine-3-glucuronide (morphine's major metabolite) were determined following single 10-mg doses of morphine sulfate in oral solution and rectal suppository. Ten patients with pain secondary to cancer were given a single 10-mg dose of oral morphine sulfate in an oral solution or rectal suppository on sequential days. Blood samples were collected at time zero and periodically for 4.5 hours after administration. Plasma concentrations of morphine and morphine-3-glucuronide were determined using liquid chromatography with electrochemical detection. Higher mean concentrations of morphine were achieved with the rectal suppository than with the oral solution at all time points, and the overall mean plasma morphine concentration for the entire 4.5-hour period was significantly higher for the rectal suppository than for the oral solution. There were no significant differences between dosage forms in mean morphine-3-glucuronide concentrations at individual time points or over the entire period. A single dose of morphine sulfate in a rectal suppository was better absorbed than in an oral solution. Further studies are needed to compare the clinical efficacy of these dosage forms under steady-state conditions.

Special report on Laetrile: the NCI Laetrile Review. Results of the National Cancer Institute's retrospective Laetrile analysis.

The National Cancer Institute, in response to widespread public interest, undertook a retrospective analysis of Laetrile treatment. Only cases thought to have shown objective benefit from Laetrile were solicited by mail request to 385,000 physicians and 70,000 other health professionals and by direct contact with pro-Laetrile groups. Although it is estimated that at least 70,000 Americans have used Laetrile, only 93 cases were submitted for evaluation. Twenty-six of these Laetrile cases had to be eliminated because of insufficient documentation, and an equal number of conventionally treated cases selected from the institute's files were added to the records to be analyzed. A panel of 12 oncologists, who had no knowledge of the actual treatments given, was then asked to evaluate the results of 160 courses of treatment (68 Laetrile, 68 chemotherapy, 24 "no treatment") in the abstracted records from 93 patients. The panel judged six Laetrile courses to have produced a response (two complete and four partial). These results allow no definite conclusions supporting the anti-cancer activity of Laetrile. The National Cancer Institute will use the data in deciding if further study is needed.

"I'm sorry to tell you ..." physicians' reports of breaking bad news.

In this investigation the authors assessed what physicians do when planning for and delivering bad news to patients. Seventy-three physicians responded to a series of statements about the behaviors, thoughts, and feelings they might have had while preparing for and delivering bad medically-related news. Data were also obtained about how well they thought the transaction had gone, how much stress they had experienced, and what they thought the experience was like from the patient's perspective. Physicians reported that these transactions were only moderately stressful, with 18.1% and 18.7% indicating that preparation stress or delivery stress, respectively, were above the midpoint on the scale. Slightly over 42% of the sample indicated that the stress they experienced lasted from several hours to three or more days. Thirty-six delivery-related statements were typical (with endorsement rates of at least 80% in a given direction) for at least one of the two recall groups.

Double-blind crossover trial of droperidol, metoclopramide, and prochlorperazine as antiemetics in cisplatin therapy.

Droperidol, metoclopramide, and prochlorperazine were compared in a double-blind crossover trial to determine their relative effectiveness in preventing and controlling the nausea and vomiting caused by cisplatin-containing chemotherapy. Twenty-five patients receiving cisplatin-containing chemotherapy for various malignancies were entered into this trial with 14 patients completing the three-drug randomization sequence. This was the patient's first exposure to cisplatin. Each antiemetic was administered in a diluted 50 ml i.v. injection over 15 minutes beginning 0.5 hour before cisplatin and 1.5, 3.5, 5.5, and 8.5 hours after cisplatin. Dosages of antiemetics for doses of cisplatin greater than or equal to 100 mg/sq m were droperidol 2.5 mg, metoclopramide 2 mg/kg, or prochlorperazine 5 mg in each infusion. For doses of cisplatin less than 100 mg/sq m, the dosages were droperidol 2.5 mg for the first two doses and 1.25 mg for subsequent doses, metoclopramide 1 mg/kg, or prochlorperazine 5 mg for each dose. The median number of emetic episodes for the first 24 hours were as follows: droperidol 3.2; metoclopramide 1.8; prochlorperazine 3.7. There was a significant difference in number of emetic episodes demonstrating antiemetic superiority of metoclopramide over both droperidol and prochlorperazine. For these 14 patients completing the trial, eight preferred metoclopramide, two preferred prochlorperazine, one preferred droperidol, and three had no preference. At the doses used in this study, the antiemetic efficacy of metoclopramide was superior to either droperidol or prochlorperazine.

Evaluation of the continuous infusion of etoposide plus cisplatin in metastatic breast cancer. A collaborative North Central Cancer Treatment Group/Mayo Clinic phase II study.

A prospective clinical trial was done to evaluate the efficacy and toxicity of cisplatin plus etoposide (VP-16) in patients with breast cancer who failed one previous chemotherapy regimen for advanced disease or relapsed within 12 months of adjuvant chemotherapy. Partial responses occurred in 11 of 44 evaluable patients (25%; 95% confidence interval (CI), 13% to 40%). The median time to disease progression in responding patients was 4 months (range, 3 to 6+ months), whereas the median time to disease progression and survival for all patients who were treated were 3 and 7 months, respectively. There was marked toxicity related to this protocol treatment including pancytopenia, gastrointestinal upset, and renal insufficiency. Two treatment-related deaths occurred; one from sepsis and one from renal failure. Thus, this regimen, as second-line chemotherapy for women with metastatic breast cancer, resulted in moderate, short-term, antitumor activity at the expense of marked toxicity.