Relief of Neuropathic Pain Through Epidermal Growth Factor Receptor Inhibition: A Randomized Proof-of-Concept Trial.

OBJECTIVE: Case reports and a case series have described relief of neuropathic pain (NP) after treatment with epidermal growth factor receptor inhibitors (EGFR-Is). These observations are supported by preclinical findings. The aim of this trial was to explore a potential clinical signal supporting the therapeutic efficacy of EGFR-Is in NP. METHODS: In a proof-of-concept trial using a randomized, double-blind, placebo-controlled design, 14 patients with severe, chronic, therapy-resistant NP due to compressed peripheral nerves or complex regional pain syndrome were randomized to receive a single infusion of the EGFR-I cetuximab and placebo in crossover design, followed by a single open-label cetuximab infusion. RESULTS: The mean reduction in daily average pain scores three to seven days after single-blinded cetuximab infusion was 1.73 points (90% confidence interval [CI] = 0.80 to 2.66), conferring a 1.22-point greater reduction than placebo (90% CI = -0.10 to 2.54). Exploratory analyses suggested that pain reduction might be greater in the 14 days after treatment with blinded cetuximab than after placebo. The proportion of patients who reported ≥50% reduction in average pain three to seven days after cetuximab was 36% (14% after placebo), and comparison of overall pain reduction suggests a trend in favor of cetuximab. Skin rash (grade 1-2) was the most frequent side effect (12/14, 86%). CONCLUSIONS: This small proof-of-concept evaluation of an EGFR-I against NP did not provide statistical evidence of efficacy. However, substantial reductions in pain were reported, and confidence intervals do not rule out a clinically meaningful treatment effect. Evaluation of EGFR-I against NP therefore warrants further investigation.

Palliative pelvic radiotherapy for symptomatic rectal cancer - a prospective multicenter study.

BACKGROUND AND PURPOSE: Palliative pelvic radiotherapy (PPRT) is used to treat locally advanced rectal cancer (RC) although symptomatic effects and toxicities are poorly documented. Aims were to evaluate symptom severity, quality of life (QOL) and toxicity after PPRT. MATERIAL AND METHODS: Fifty-one patients with symptomatic primary or recurrent RC prescribed PPRT with fractions of 3 Gy to 30-39 Gy were included. Primary outcome was severity of target symptoms (TS) 12 weeks after PPRT. Pelvic symptom burden, toxicity, and QOL were assessed. Response was defined as patient-reported TS improvement or resolution. RESULTS: Pain (n = 24), rectal dysfunction (n = 16), and hematochezia (n = 9) were the most common TSs. Overall response rate among evaluable patients 12 weeks after PPRT was 28/33 (85%). Eighteen patients did not complete the study follow-up, 16 due to deteriorating health. TS responses were 10/13 (77%) for pain, 9/10 (90%) for rectal dysfunction, and 8/8 for hematochezia. Non-target pelvic symptom severity decreased and median QOL scores remained stable. There was no grade 4 toxicity. Median survival was nine months. CONCLUSIONS: In the majority of patients with symptomatic primary or recurrent RC, PPRT with 30-39 Gy contributes to pelvic symptom relief, with little toxicity. Patients prescribed PPRT of RC have limited life expectancy. Future studies should investigate simplification of PPRT.

Incidence and risk factors of venous thromboembolism (VTD) in patients with amyloidosis.

BACKGROUND: Coagulation problems in amyloidosis are historically associated with bleeding tendencies (mostly Factor X abnormalities). Increased clotting was observed in isolated cases diagnosed with low-grade disseminated intravascular coagulation (DIC). Problem of venous thromboembolic disaease (VTD) in amyloidosis was not systematically investigated. METHODS: We evaluated frequency of VTD and risk factors for VTD in 56 consecutive amyloidosis patients with a documented disease evaluated and followed up at our Center from 1991-2001. Data was collected in 5 categories: (a) demographics, (b) disease and treatment, (c) thrombosis case information, (d) major risk factors for thrombosis and (e) baseline laboratory data. Univariable correlates of VTD were assessed using Kaplan-Meier analysis and Cox proportional hazards analysis. RESULTS: Mean age of the patients was 67 (years range 21-83). Male/female percentage ratio was 70/30. 29% of the patients had high creatinine level (> 1.4 mg/dl). Personal or family history of VTD was recorded in 2 and 0% of patients, respectively. Known hypercoagulable state was present in 1 patient (2%). 8% of patients were smokers. Of 56 patients, 6 developed VTD (11%). Median time from diagnosis of amyloidosis to VTD was 12.5 month (range 1-107). Treatment was given within a median of 1 month (range 0-4) from the development of thrombosis. Only sites of VTD were lower extremities. No cases were associated with I.V. line. 1 case (17%) was identified postoperatively. We identified several univariable correlates of VTD in amyloid patients, including greater age at diagnosis (HR-2.99, P = .041), personal history of DVT (HR-47.7, P = .006) and immobility (HR-11.78, P = .006). Presence of circulating serum M-protein had protective role in our analysis (HR-.08, P = .031). There was no correlation with the type of treatment patients were receiving. CONCLUSION: Risk for thromboembolic diseases in patients with amyloidosis is similar to one previously described for multiple myeloma. Additional studies with higher number of thromboembolic events could help to further elucidate risk factors for VTD in this population of patients.

Patient reported outcomes of symptoms and quality of life among cancer patients treated with palliative pelvic radiation: a pilot study.

BACKGROUND: There is limited high-quality research investigating the efficacy of palliative radiation (PPR) with regard to symptoms and quality of life (QOL) among cancer patients with pelvic soft tissue tumors. As a result, clinicians are left with mainly retrospective studies, without reliable data on which to base treatment decisions. As a first step of a subsequent analysis of PPR's efficacy, we aimed to determine whether it is feasible to prospectively measure symptoms and QOL among patients treated with PPR. A secondary aim was to explore patients' willingness to answer existential questions in the setting of palliative pelvic radiation. METHODS: Patients referred for palliative radiation of soft-tissue pelvic tumors were invited to enter the study. Symptoms were scored by study physicians and QOL was assessed by the EORTC QLQ C-30 questionnaire and site specific modules (PR25, CR38 or BL24) prior to start of radiation and 6 and 12 weeks after its completion. In addition, patients answered existential questions at each of the study visits. A radiation therapist was available to participants in order to answer their questions and ensure that questionnaires were completed. FINDINGS: Five female and 17 male patients with prostate cancer (14), colorectal cancer (5) and bladder cancer (3) were included in the study. The median age of the participants was 75 years (range 62-90). Twenty patients were still in the study at the 6-week follow-up and 18 patients at the 12-week follow-up. Twenty-one patients had valid responses within all the EORTC QLQ C-30 scales at baseline, 20/20 at the 6-week follow-up and at the 12-week follow-up 17/18 patients still in the study had valid responses within all scales. This level of response was similar in the site-specific modules and among the existential questions. DISCUSSION: Among patients with prostate, colorectal and bladder cancer, compliance to questionnaires assessing symptoms, QOL and existential questions 6 and 12 weeks after PPR is sufficient to enable evaluation in a larger and more homogeneous patient group in order to reach clinically valid conclusions as to the efficacy of PPR.

Monoclonal gammopathy of undetermined significance and multiple myeloma are associated with an increased incidence of venothromboembolic disease.

BACKGROUND: Venous thromboembolic disease (VTD) is a recently recognized complication of thalidomide in combination therapy for patients with multiple myeloma (MM). The authors assessed the frequency of VTD and its risk factors in 612 consecutive patients with plasma cell dyscrasia (PCD) who were evaluated and followed from 1991 to 2001. METHODS: In the current study, 404 patients were diagnosed with multiple myeloma (MM), 174 with monoclonal gammopathy of undetermined significance (MGUS), and 34 with other forms (excluding amyloidosis). Univariable correlates of VTD were assessed using Kaplan-Meier analysis and Cox proportional hazards analysis. RESULTS: The authors identified several univariable correlates of VTD in patients with MGUS, including a family and medical history of VTD, immobility, low serum albumin level, and high leukocyte count. Patients with MGUS with immunoglobulin (Ig) G monoclonal immunoglobulin were found to be less prone to develop VTD. In patients with MM, a family and medical history of VTD and the presence of a hypercoagulable state were factors identified in univariable analysis to be associated with an increased risk of VTD. In patients with MM, for each unit increase in serum albumin, the risk of VTD was lower. The type of the treatment regimen did not appear to correlate with the development of VTD. CONCLUSIONS: In the current study, the risk for thromboembolic diseases among patients with PCD was increased compared with the risk in the general population. Further studies are necessary to define the mechanisms involved.