Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients.

PURPOSE: A minority of cancer survivors develops long-term postsurgical neuropathic pain. Based on evidence that capsaicin, the pungent ingredient in hot chili peppers, might be useful for treating neuropathic pain, we developed the present clinical trial. PATIENTS AND METHODS: Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study. After stratification, patients were to receive 8 weeks of a 0.075% capsaicin cream followed by 8 weeks of an identical-appearing placebo cream, or vice versa. A capsaicin/placebo cream was to be applied to the painful site four times daily. Treatment evaluation was performed by patient-completed weekly questionnaires. RESULTS: During the first 8-week study period, the capsaicin-cream arm was associated with substantially more skin burning, skin redness, and coughing (P < .0001 for each). Nonetheless, treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin. The capsaicin cream arm had substantially more pain relief (P = .01) after the first 8 weeks, with an average pain reduction of 53% versus 17%. On completion of the 16-week study period, patients were asked which treatment period was most beneficial. Of the responding patients, 60% chose the capsaicin arm, 18% chose the placebo arm, and 22% chose neither (P = .001). CONCLUSION: A topical capsaicin cream decreases postsurgical neuropathic pain and, despite some toxicities, is preferred by patients over a placebo by a three-to-one margin among those expressing a preference.

Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.

PURPOSE: To determine the efficacy of transdermal clonidine for alleviating tamoxifen-induced hot flashes in women with a history of breast cancer. PATIENTS AND METHODS: A randomized, double-blind, crossover design was used in this prospective study. Women with a history of breast cancer who were receiving tamoxifen and suffering from hot flashes were potentially eligible for this protocol study. RESULTS: Clonidine did reduce hot-flash frequency to a degree that was statistically impressive (P < .0001), but clinically moderate (20% reduction from baseline). It also decreased hot-flash severity (P = .02, 10% reduction from baseline). Clonidine was related to increased mouth dryness (P < .001), constipation (P < .02), itchiness under the patch (P < .01), and drowsiness (P < .05). CONCLUSION: Better means are needed to alleviate hot flashes among patients in whom estrogen therapy is contraindicated.

Randomized comparison of four tools measuring overall quality of life in patients with advanced cancer.

PURPOSE: We report on a clinical trial developed to compare four different instruments that provide overall quality-of-life (QOL) scores, ranging from a simple, one-item instrument to more detailed instruments. Two issues addressed were (1) Will QOL tools suffer from missing data when used in a community-based cooperative group setting?, and (2) Are there additional data generated by a more detailed multiitem instrument over that provided by a single-item global QOL question? MATERIALS AND METHODS: A four-arm randomized trial was designed to compare four instruments that provide overall QOL scores in patients with advanced colorectal cancer. Patients and physicians completed the single-item Spitzer Uniscale (UNISCALE) at baseline and monthly. Patients were randomly assigned to complete, in addition, either the 22-item Functional Living Index-Cancer (FLIC), the five-item Spitzer QOL index (QLI), a picture-face scale (PICT), or nothing else. RESULTS: A total of 128 patients were randomized. Greater than 90% complete QOL data were obtained. There was strong correlation, concordance, and criterion-related validity among all four patient-completed tools. The UNISCALE had a greater decrease over time than did the FLIC (P=.005), which suggests a greater sensitivity; the UNISCALE was similar to the QLI and the PICT in this regard. Physicians provided lower UNISCALE scores than patients. Results supported the hypothesis that QOL is prognostic for survival. CONCLUSION: Patients can effectively complete QOL tools in a cooperative group setting with proper education of health care providers and patients. A simple single-item tool (UNISCALE) appears to be appropriate to obtain a measure of overall QOL.

Transdermal fentanyl in the management of cancer pain in ambulatory patients: an open-label pilot study.

We performed an open-label pilot study to define analgesic efficacy, acceptability, and toxicity of transdermal fentanyl in an ambulatory population of patients with cancer pain. Our 7-day study included 35 patients, all of whom had failed a trial of an opioid analgesic conventionally used for moderate pain. Patients received either a 25 micrograms/hr or 50 micrograms/hr fentanyl transdermal patch depending on prior opioid dose. Pain was measured daily utilizing visual analogue (VAS) and categorical (CAT) scales. Hours of nighttime sleep, quality of life, toxicities, and use of rescue medication were also assessed. There was a 24%-29% reduction in mean VAS and CAT pain scores as compared with the baseline and a 25% increase in mean hours of nighttime sleep. Fifty-nine percent of those patients responding (46% of all study patients) were satisfied to very satisfied with the analgesia provided by transdermal fentanyl. Six percent of all study patients were not at all satisfied with the pain relief obtained. Toxicities were similar to those seen with other opioids. No patient developed severe sedation or respiratory depression. The 25-50 micrograms/hr patch appears to be a safe starting dosage in ambulatory patients previously receiving opioids conventionally used for moderate pain.

Trial of a topically administered local anesthetic (EMLA cream) for pain relief during central venous port accesses in children with cancer.

Procedure-related pain is a significant problem for many children receiving cytotoxic chemotherapy. In an effort to lessen this toxicity, we studied the efficacy and safety of administering topical local anesthesia using EMLA cream in 47 evaluable children with cancer undergoing implanted central venous port injections. Children (< 21 years old) scheduled to undergo repeated venous access procedures were selected for study. A placebo-controlled, randomized, double-blind, crossover study design was utilized. Statistically significant decreases in pain intensity scores (P < 0.002) were recorded by both children and investigators during the use of EMLA cream as compared with placebo. There was a good correlation between pain scores recorded by both patients and health care providers using both visual analog scales and categorized pain measurement tools. The topical application of EMLA cream 5% provides highly effective superficial anesthesia, and promises to be extremely useful for pain relief during percutaneous access procedures in cancer patients.

Epidemiologic features of pain in pediatric cancer patients: a co-operative community-based study. North Central Cancer Treatment Group and Mayo Clinic).

The prevalence, etiology, and management of pain in pediatric cancer patients seen at the Mayo Clinic and member institutions of the North Central Cancer Treatment Group were assessed. Participating centers, including both primary care and referral institutions, surveyed all patients seen during a 1-week period (Monday through Friday); procedure-related pain was excluded. Of the 160 children surveyed, 28 reported pain of which 57.8% was related to a side effect of anticancer treatment, 21.1% was unrelated to the malignancy, and 21.1% arose directly from the cancer. Pain intensity assessment was performed by both health-care professional and patient using a variety of measurement tools. Correlation between assessors was close except in young children. The predominance of treatment-related rather than cancer-related pain differs from results in series in adult cancer patients.

Sweet syndrome in a patient with osteosarcoma.

Neutrophilic dermatosis (Sweet syndrome) is a rare condition characterized by painful indurated cutaneous plaques infiltrated with mature neutrophils and may be accompanied by fever, granulocytosis, arthritis, and conjunctivitis. It is associated with various malignant and preneoplastic states, the most common being leukemia and myeloproliferative disorders. Its association with solid tumors is infrequent. The case described here represents, to our knowledge, the first report of Sweet syndrome in a patient with osteogenic sarcoma, a primary tumor of bone arising from mesenchymal cells.

The treatment of cancer pain in children.

In summary, expertise is currently available to successfully manage most pediatric cancer pain; it behooves the responsible physician to be sufficiently familiar with the available methodology and to appropriately deliver state-of-the-art management to the child to ensure optimal care.

Rhabdomyosarcoma. A new classification scheme related to prognosis.

We classified 159 cases of rhabdomyosarcoma (RMS) according to the conventional scheme adopted by the World Health Organization and a modified conventional scheme established at the National Cancer Institute (NCI), Bethesda, Md. The major modification in the NCI scheme was the inclusion of compact round-cell RMS with scant myogenesis in the group of alveolar RMS despite lack of an alveolar architecture. These tumors were previously considered to be embryonal RMS, but their cytologic features are quite different from those seen in embryonal RMS and are indistinguishable from those encountered in alveolar RMS. These tumors are referred to as "solid alveolar RMS." Survival curves were constructed with the method of Kaplan-Meier and compared with the unstratified and stratified methods of Mantel-Haenszel (with stratification factors being stage, site, and age) and with the Cox regression analysis. Both histologic schemes showed a statistically significant prognostic value in unstratified analyses, but the NCI scheme demonstrated prognostic value even in stratified analyses and in the Cox regression analysis in our series of cases. The data indicate that the NCI scheme can serve as a highly predictive, independent prognostic factor in RMS and that the alveolar category should be expanded to include the solid round-cell RMS, even in the absence of a classic alveolar architecture.

Septicemia in childhood malignancy. Analysis of 101 consecutive episodes.

One hundred one consecutive episodes of blood-culture-positive infection were evaluated in 83 children with malignancy between 1972 and 1977. Eighty-two per cent occurred in relapse, and 75% developed when the absolute neutrophil count was less than 500 per microliters. Forty per cent were fatal. Forty-five per cent of the episodes occurring in relapse and 17% occurring in remission were fatal. Of 88 cases of single-organism infection, 46% were due to gram-positive organisms with a 13% mortality (of these, 28% were due to Staphylococcus aureus with a 4% mortality); 52% were due to gram-negative organisms with a 52% mortality; and two episodes were due to fungal organisms with no fatalities. Multiple-organism infection occurred 13 times, of which 11 episodes were fatal. The authors' data confirm observations by others that the organisms most commonly causing blood-culture-positive infection in children with malignancy are S. aureus and Escherichia coli and that infection due to gram-positive organisms, particularly S. aureus, is less than frequency fatal.

Postdural puncture headache in pediatric oncology patients.

This prospective cohort study determined the incidence and risk factors for development of postdural puncture headache (PDPH) in children after lumbar puncture (LP). Eighty-six children were enrolled. LPs were performed with use of 22-gauge spinal needles with the bevel oriented parallel to the long axis of the spine. Follow-up telephone interviews and patients' diary of symptoms were collected. Headache brought on by sitting up and relieved by lying down was defined as PDPH. Of the 80 who completed the study, six (8%) developed PDPH. Two (3%) were less than 6 years old and four (5%) were 6 to 12 years of age. Children with a history of headache following a previous LP were nine times as likely to experience PDPH. PDPH occurs not infrequently in children. A prior history of headache is a predisposing factor.

Staphylococcus aureus sepsis in childhood malignancy.

Forty-five episodes of Staphylococcus aureus septicemia occurred in 44 children with malignant neoplasms over a seven-year period. The frequent findings at diagnosis were fever, neutropenia, and an active malignant process. Twenty-six (58%) of 45 episodes had a primary focus of infection. Multiple-organism sepsis occurred four times; three episodes were fatal. Only one patient with single-organism S aureus sepsis died (a mortality of 2%). Direct infectious complications occurred in nine (20%) of 45 episodes. Endocarditis and osteomyelitis were not seen as complications of S aureus sepsis.

Smoking patterns and cessation motivations during adolescence.

With increased knowledge of effective prevention of adolescent smoking, there is a concomitant lack of research on effective adolescent smoking cessation. This study surveyed 77 adolescents (mean age 15.8 years) at a youth detention center in Seattle, Washington, about smoking patterns, cessation attempts, and motivations as well as withdrawal symptoms from nicotine. The results revealed that the majority of smokers had previously attempted smoking cessation (72%). The most common reasons for wanting to quit were for health concerns. Only 30.8% abstained for more than 1 month, and 35.9% abstained for less than 3 days. Nicotine craving was the most severe and most commonly reported withdrawal symptom.

Variation in morphine pharmacokinetics in children with cancer.

Morphine plasma concentrations were determined in 19 children with cancer. A single dose of morphine, 0.09-0.15 mg/kg, was given intravenously over 3-5 min. The plasma concentrations of morphine ranged from 23 to 472 ng/ml at 10 min and from 6.1 to 20.8 ng/ml at 60 min after morphine administration. The morphine plasma concentration exceeded the reported average analgesic concentration of about 20 ng/ml in only 1 patient at 60 min and subsequently declined further except for 4 patients in whom plasma levels exhibited a secondary peak. The pharmacokinetics of morphine was studied in 6 children. The total clearance of morphine ranged from 9.03 to 53.4 ml/min/kg. The apparent volume of the central compartment and the apparent volume of distribution at steady state ranged from 0.17 to 1.10 and from 2.06 to 7.86 l/kg, respectively. The elimination half-life ranged from 0.86 to 7.55 h. These data indicate that an interindividual variation in morphine pharmacokinetics is one factor responsible for varying dosage requirements in children with cancer.

Narcotic withdrawal syndrome in young adults after the therapeutic use of opiates.

Five young adults with malignant neoplasms developed symptoms of narcotic withdrawal six to 48 hours after the abrupt discontinuation of narcotic therapy that had been administered for six to 21 days. The symptoms, which included agitation, irritability, muscular jerks, abdominal pain, diarrhea, burning sensations, "gooseflesh," and itching, rapidly resolved when narcotic therapy was reinstituted. Four patients were then successfully weaned from opiates without recurrence of their withdrawal symptoms; the fifth patient continues to receive methadone hydrochloride treatment for continuing pain.

Pulmonary valvulotomy in Factor XI deficiency.

This is the first reported case in the English literature of Factor XI deficiency in a child from India. He underwent open-heart surgery and pulmonary valvulotomy without excessive or delayed hemorrhage using plasma infusion to sustain Factor XI levels at about 40% of normal before, and for 10 days after surgery. The management of this child is presented as an approach to patients with Factor XI deficiency who require major surgery.