A pilot study of long-acting octreotide for symptomatic malignant ascites.

BACKGROUND: Effective, non-invasive, palliative strategies for symptomatic malignant ascites are unavailable. This trial explored whether octreotide, an inhibitor of vascular endothelial growth factor, a putative mediator of ascites, prolongs the interval to next paracentesis. METHODS: After a baseline paracentesis and a test of short-acting agent, patients with symptomatic ascites were randomly assigned to long-acting octreotide (Sandostatin LAR®) depot 30 mg intramuscularly every month versus 0.9% sodium chloride administered similarly. Patients were then monitored for recurrent, symptomatic ascites. RESULTS: Thirty-three patients were enrolled: 16 assigned to the octreotide and 17 to the control arm. The median time to next paracentesis was 28 and 14 days in the octreotide and placebo arm, respectively (p = 0.17). After adjustment for extracted ascites volume and abdominal girth change, no statistically significant difference between the groups was observed (hazard ratio = 0.52, with a 95% confidence interval of 0.21-1.28; p = 0.15, per Cox model). Octreotide-treated patients described less of abdominal bloating (p = 0.01), abdominal discomfort (p = 0.02), and shortness of breath (p = 0.007) at one month, although other quality of life symptoms were comparable between the arms. Long-acting octreotide was reasonably well tolerated. CONCLUSION: As prescribed in this trial, octreotide did not seem effective in prolonging the time to next paracentesis, although improvements in symptoms suggest that vascular endothelial growth factor inhibition merits further investigation.

The relationship between numbness, tingling, and shooting/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as measured by the EORTC QLQ-CIPN20 instrument, N06CA.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is characterized by numbness, tingling, and shooting/burning pain. This analysis was performed to describe the relationship between numbness, tingling, and shooting/burning pain in patients with CIPN, as reported using the EORTC QLQ-CIPN20 (CIPN20). METHODS: Baseline CIPN20 data were provided for all patients on a prospective trial designed to treat patients with bothersome CIPN. Baseline frequencies for the items on the CIPN20 are primarily described by descriptive statistics and histograms, with correlational analyses between individual items. RESULTS: A majority of the 199 patients accrued to this study reported "quite a bit" to "very much" numbness (57%) or tingling (63%) in the hands compared to "a little" or "not at all" (numbness (43%), tingling (38%)). Fewer patients reported "quite a bit" to "very much" shooting/burning pain in the hands (18%). Numbness and tingling in the hands were highly correlated (r = 0.69), while neither were highly correlated with shooting/burning pain. Similar results were observed in the feet. More severe ratings for tingling and shooting/burning pain were ascribed to the lower extremities, as opposed to the upper extremities. CONCLUSIONS: In patients with CIPN, severe sensory neuropathy symptoms (numbness, tingling) commonly exist without severe neuropathic pain symptoms (shooting/burning pain), while the reverse is not common. Symptoms in the feet should be evaluated distinctly from those in the hands as the experience of symptoms is not identical, for individual patients, in upper versus lower extremities.

A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome chronic symptom that has no proven pharmacologic treatment. The purpose of this double-blind randomized placebo-controlled trial was to evaluate a novel compounded topical gel for this problem. METHODS: Patients with CIPN were randomized to baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) versus placebo (PLO) to determine its effect on numbness, tingling, pain, and function. The primary endpoint was the baseline-adjusted sensory subscale of the EORTC QLQ-CIPN20, at 4 weeks. RESULTS: Data in 208 patients reveal a trend for improvement that is greater in the BAK-PLO arm over placebo in both the sensory (p = 0.053) and motor subscales (p = 0.021). The greatest improvements were related to the symptoms of tingling, cramping, and shooting/burning pain in the hands as well as difficulty in holding a pen. There were no undesirable toxicities associated with the BAK-PLO and no evidence of systemic toxicity. CONCLUSION: Topical treatment with BAK-PLO appears to somewhat improve symptoms of CIPN. This topical gel was well tolerated, without evident systemic toxicity. Further research is needed with increased doses to better clarify the clinical role of this treatment in CIPN.

Phase III randomized, double-blind study of maintenance CAI or placebo in patients with advanced non-small cell lung cancer (NSCLC) after completion of initial therapy (NCCTG 97-24-51).

PURPOSE: This study assessed whether maintenance therapy with carboxyaminoimidazole (CAI), compared to placebo, prolonged overall survival in stage IIIB/IV NSCLC patients who had tumour regression or stable disease after treatment with one chemotherapy regimen. METHODS: After completion of chemotherapy, patients were randomized to receive daily oral CAI at 250mg or placebo. Treatment continued until patient refusal, disease progression or unacceptable adverse event (AE). Quality of life (QOL) was assessed by UNISCALE and Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L). RESULTS: Registration was halted early for slow accrual (targeted 360, randomized 186: 94 CAI, 92 placebo). All patients were off active treatment at time of analyses. Non-haematologic AEs (primarily grade 1, 2) observed significantly more often in the CAI group included fatigue (54.5% versus 29.3%), anorexia (31.1% versus 13.0%), nausea (62.2% versus 30.4%), vomiting (32.2% versus 14.1%), neurosensory (60.0% versus 44.6%) and ataxia (33.3% versus 16.3%). Patients discontinued treatment for AEs, death on study or refusal more often in the CAI group (36.0% versus 8.7%, p<0.0001). No significant differences in survival or time to progression were observed (median: CAI versus placebo: 11.4 months versus 10.5 months, log rank p=0.54; 2.8 months versus 2.4 months, log rank p=0.50). More patients receiving CAI reported a clinically significant (10-point) decline in QOL particularly on the functional (58% versus 37%, p=0.05) construct of FACT-L and UNISCALE (72% versus 51%, p=0.04). CONCLUSION: The addition of CAI following chemotherapy does not provide clinical benefit or improvement in QOL over placebo in advanced NSCLC.

The prevalence of weight concerns in a smoking abstinence clinical trial.

Recent research has demonstrated there is a high prevalence of weight concerns in smokers and that smokers with weight concerns may respond poorly to treatment for tobacco dependence. Most studies have focused only on females or have consisted of small samples. In this study of a 12-week randomized trial of nicotine inhaler, bupropion or both for smoking cessation, 50% of the 1012 female smokers and 26% of the 680 male smokers, at study entry, were weight concerned. In examining the impact of weight concerns on the 12-week point-prevalence smoking abstinence, 26% of non-weight-concerned smokers quit smoking compared to 22% of weight-concerned smokers (p=0.06). This study, which includes a large sample of both genders, provides further evidence that approximately half of females who are seeking smoking cessation treatment are weight concerned and that one quarter of male smokers are weight concerned. Additionally, being weight concerned may impact the short-term success rates of stopping smoking using pharmacotherapy.

Phase III comparison of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) vs. doxorubicin and cisplatin (AC) in women with advanced primary or recurrent metastatic carcinoma of the uterine endometrium.

OBJECTIVES: The North Central Cancer Treatment Group Phase III trial compared efficacy of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with doxorubicin plus cisplatin (AC) for patients with advanced endometrial cancer. METHODS: Twenty-eight patients were randomly assigned to treatment with doxorubicin 30 mg/m2 + cisplatin 70 mg/m2 IV q 4 weeks vs. methotrexate 30 mg/m2 IV days 1, 15, and 22, vinblastine 3 mg/m2 IV days 2, 15, and 22, doxorubicin 30 mg/m2 IV day 2, and cisplatin 70 mg/m2 day 2 of a 4-week cycle. The trial was terminated prematurely due to slow accrual. RESULTS: Prior to early closure of the protocol, there were 15 patients entered on the AC regimen and 13 to the MVAC regimen. There were 3 PR (20%) for AC and 3 CR (23%) and 3 PR (23%) for MVAC. Median PFS was 4.0 months for AC and 6.9 months for MVAC. Median survival was 13.2 months for AC and 16.8 months for MVAC. Toxicity was substantial for MVAC vs. AC with severe leukopenia seen in 69% vs. 33% of patients and severe thrombocytopenia 23% vs. 0%. No treatment-related deaths were seen. DISCUSSION: MVAC and AC are active regimens in the treatment of advanced/recurrent or metastatic endometrial cancer. The premature closure of the protocol resulted in small patient numbers that left the protocol underpowered to address the primary objective of demonstrating improved CR rate for MVAC over AC. MVAC has substantial toxicity compared to AC and is not substantially superior to AC. MVAC cannot be considered as a standard for treatment in this patient population.