Elucidating nuclear motions in a plant sunscreen during photoisomerization through solvent viscosity effects.

We explore the effects of solvent viscosity on the trans-cis photoisomerization of sinapoyl malate, which is utilized as a sunscreen molecule in plants. Our results demonstrate that viscosity has a significant effect on the timescale for isomerization, providing insight into the nuclear motions involved. The ramifications of these findings are discussed with reference to sinapoyl malate's in vivo photoprotection properties.

Common cancers--immunotherapy and multidisciplinary therapy: Parts III and IV.

The refractoriness of many solid tumors to cytotoxic chemotherapy has led to the exploration of new therapeutic modalities, including immunotherapy. Immunotherapy does not have a direct cytotoxic effect on the cancer cell but is an attempt to promote rejection of the tumor by the host, chiefly through the cellular arm of the immune system. The clinical success with immunotherapy (primarily adoptive immunotherapy) among patients with unresectable malignant melanoma and cancer of the kidney has not been marked by the large numbers of patients responding but by occasional dramatic effectiveness of therapy for these cancers, which usually are refractory to chemotherapy. Long-lasting responses and even complete disappearance of all known metastases are possible for a small percentage of patients with melanoma or renal cell carcinoma who undergo immunotherapy. A reasonable approach for patients with good performance status (no symptoms or ambulatory with symptoms but not bedridden) is entrance to clinical trials, especially trials examining adoptive or active immunotherapy for melanoma or adoptive immunotherapy for renal cancer. The overall treatment of patients with cancer has changed. Primary-care physicians detect almost all cancers. The days when "taking it out" is the best we could offer a patient are over. As we learn more about the use of adjuvant or neoadjuvant chemotherapy and radiation therapy, it is likely one or both of these modalities will be incorporated into the treatment of additional solid tumors previously managed solely with surgical resection. Increasingly, additional therapy is being given for earlier-stage disease as we define how to maximize the potential for cure with minimal toxicity. Many new therapies are on the horizon, including the use of noncytotoxic treatments as an adjunct to a surgical procedure. Such therapies include the use of angiogenesis inhibitors, tumor vaccines, and immunotherapy. Now and in the future, patients will be best served when treated in an environment that can integrate medical, surgical, and radiation oncology actively.

Active specific immunotherapy of metastatic melanoma with an antiidiotype vaccine: a phase I/II trial of I-Mel-2 plus SAF-m.

PURPOSE: To determine the toxicity and immunologic activity of an antiidiotype melanoma vaccine that consists of monoclonal antibody I-Mel-2 (MELIMMUNE-2, IDEC Pharmaceuticals, La Jolla, CA) and an immunologic adjuvant SAF-m. PATIENTS AND METHODS: Twenty-six patients with metastatic melanoma, 17 of whom had previously received chemotherapy, were given 2 mg of I-Mel-2 and either 100 micrograms (n = 6) or 250 micrograms (n = 20) of SAF-m. Antiidiotype vaccine was given intramuscularly (IM) biweekly for 4 weeks, and then bimonthly until disease progression. Human antimurine antibodies (HAMA), anti-I-Mel-2 antibodies, and specific antibody (Ab)3 against the melanoma epitope mimicked by the vaccine were titrated before treatment, biweekly from weeks 4 to 12, and every 4 to 8 weeks thereafter. Computed tomographic (CT) scans of the chest, abdomen, and pelvis and magnetic resonance imaging (MRI) of the brain were obtained before and bimonthly during treatment to evaluate responses. RESULTS: Elevated titers of human antimouse antibodies and anti-I-Mel-2 antibodies were associated with clinical antitumor effect (P = .02 and P = .05, respectively). Ab3 was absent in most patients, but was found in the best clinical responder. Fever, myalgias/arthralgias, fatigue, nausea, and headaches were the most common toxicities. Grade III myalgias/arthralgias and headaches required dose reduction of SAF-m in eight patients at the 250-microgram dose. No treatment-related death occurred. Six patients had an antitumor effect: one complete response in liver and lung, two minor responses, and three stable disease. The patient with a complete response has survived nearly 5 years. CONCLUSION: I-Mel-2 antiidiotype vaccine was safe, tolerated best at the 100-microgram dose of SAF-m, and had immunologic and clinical activity.

Alpha interferon-2b, leucovorin, and 5-fluorouracil (ALF) in non-small cell lung cancer.

Eighteen patients with non-small cell lung cancer (NSCLC) who had previously received no systemic chemotherapy, were treated on this phase II study with interferon-alfa-2b 8 MU tiw, leucovorin 500 mg/m2 IVPB over 2 hours and 5-Fluorouracil 500 mg/m2 i.v. for 6 weeks followed by a 2-week rest. There were was no rest period for interferon. Median age of patients on this study was 63 years. Fatigue, nausea, and diarrhea were the most common toxicities. There were no grade IV toxicities and no treatment-related deaths. Seven partial responses (39%) with median duration of 4.5 months were seen. An additional patient has had stable disease/minor response for 12+ months. Median survival is 10 months. ALF has activity in NSCLC.

Weekly 5-fluorouracil and interferon-alfa-2b in metastatic cancer.

Twenty-four patients with advanced cancer were treated with 5-Fluorouracil 600 mg/m2 intravenously and interferon-alfa-2b 3 MU subcutaneously both given weekly for 6 weeks followed by a 2-week hiatus. The median age of patients treated on this study was 66 years. Mild to moderate leukopenia, nausea/emesis, and anemia were the most common toxicities. There were no treatment-related deaths and only 1 episode of grade IV toxicity (leukopenia in a patient who was receiving concurrent radiation therapy). Two complete responses, 7 partial responses and 1 prolonged minor response (pancreas cancer--12+ months) have been seen. Weekly 5-FU and interferon is well-tolerated and shows activity in selected patients with advanced cancer.

Fatigue in patients with cancer receiving interferon alpha.

Fatigue is the most frequently reported symptom of patients with cancer. The purpose of this study was to describe the experience of fatigue over time in patients with cancer receiving treatment with interferon alpha. Piper's Integrated Fatigue Model guided this study. A descriptive repeated-measures design was used. A convenience sample of 30 patients with malignant melanoma was drawn from a comprehensive cancer center in Southern California. Two instruments were used in data collection, the Symptom Distress Scale and the Piper Fatigue Scale. Study findings revealed descriptive data on patients' perceptions of the causes and remedies for fatigue while receiving active treatment for cancer. The pattern of fatigue was consistent over the five points of time during treatment, with the most extreme fatigue scores in the affective domain, followed by the sensory, temporal, total fatigue, and fatigue severity scores. The patterns and dimensions of fatigue provide implications for care of patients receiving interferon alpha, and for further investigation in the area of fatigue as a critical aspect of quality of life.

Alpha interferon, leucovorin, and 5-fluorouracil (ALF) in advanced cancer: results of a dose-finding study and evidence of activity in non-small cell lung cancer.

In a phase I trial, 17 patients were treated with 5-fluorouracil (5-FU) 500 mg/m2 and leucovorin (LV) 500 mg/m2 intravenously weekly for 6 weeks followed by 2 weeks' rest and interferon alfa-2b 1, 3, 5, 8, or 10 million units (MU) subcutaneously tiw with no rest period. The most common toxicities were fatigue (12), diarrhea (10), nausea/vomiting (7), and fever (7). The maximum tolerated interferon dose was 8 MU tiw. Fatigue and increased incidence of other toxicities rather than a single dose-limiting toxicity occurred at the next highest interferon level. ECOG grade III/IV toxicity occurred in 5 patients and included transient supraventricular tachycardia and brief seizure episode (1), dyspnea (1), decreased performance status (1), anemia requiring transfusion (1), and deep vein thrombosis (1). No toxic deaths occurred. Two patients with non-small cell lung cancer (NSCLC) had partial responses lasting 5 and 4 months. Two other patients with NSCLC had either minor response or stable disease, and 1 patient with colon cancer had a significant decline in serum CEA. The recommended alpha interferon dose is 8 MU tiw when given with this schedule of 5-FU/LV.

Phase II study of low dose cyclophosphamide and intravenous interleukin-2 in metastatic renal cancer.

Thirteen patients with metastatic renal cancer were treated in a phase II trial with interleukin-2, 21.6 million IU/m2 intravenously daily for five days on two consecutive weeks, starting 3 days after the administration of low dose cyclophosphamide 350 mg/m2 intravenously. Treatment cycles were repeated every 21 days. No responses were seen (95% Confidence Interval: 0-22%). The most common toxicities were fever, fatigue, hypotension, nausea/emesis, and myalgia/arthralgia. There were 11 episodes of Grade III toxicity including Grade III hypotension in 7 patients. Because of the significant toxicity and the lack of observed response, the study was discontinued. Cyclophosphamide and interleukin-2 at the dose and schedule used in this study has considerable toxicity and is unlikely to improve on response rates previously seen with other IL-2 based regimens in metastatic renal cancer.

Phase II trial of carbetimer in metastatic melanoma.

A phase II study of the synthetic polyelectrolyte Carbetimer 6500 mg/m2 i.v. daily for five days every 21-day cycle was conducted in patients with metastatic melanoma. No responses were seen in 18 evaluable patients. Two patients had stable disease for five months. Toxicity was generally manageable and included mild hyperphosphatemia, mild proteinuria, fatigue, pain at the injection site, and nausea. Carbetimer is inactive in metastatic melanoma at this dose and schedule.