The effect of prophylactic calcium and magnesium infusions on the incidence of neurotoxicity and clinical outcome of oxaliplatin-based systemic treatment in advanced colorectal cancer patients

Background

Peripheral sensory neurotoxicity is a frequent and potentially debilitating side effect of oxaliplatin treatment. Calcium and magnesium (Ca/Mg) infusions are frequently used to prevent this toxicity. However, concerns about a negative impact of Ca/Mg infusions on outcome have been raised. We retrospectively assessed the effect of Ca/Mg infusions on the incidence of neurotoxicity and on clinical outcome in advanced colorectal cancer (ACC) patients treated in the phase III CAIRO2 study.

Materials and methods

Seven hundred and fifty five previously untreated ACC patients were randomised between treatment with capecitabine, oxaliplatin and bevacizumab or the same combination with the addition of cetuximab. Patients were retrospectively divided into two groups: patients in the Ca/Mg⁺ group received Ca/Mg at least during their first treatment cycle, and patients in the Ca/Mg^- group did not.

Results

Seven hundred and thirty two patients were evaluable for this analysis. The Ca/Mg⁺ group consisted of 551 patients, the Ca/Mg^- group consisted of 181 patients. The incidence of all grade neurotoxicity in the Ca/Mg⁺ group and the Ca/Mg^- group was 85% and 92%, respectively (p = 0.02), and the incidence of grade ? 2 neurotoxicity was 40% and 45%, respectively (p = 0.22). The median PFS in the Ca/Mg⁺ versus Ca/Mg^- group was 10.1 versus 10.7 months (p = 0.92), the median OS was 19.8 versus 20.7 months (p = 0.10), and the response rate was 43.1% versus 50% (p = 0.11), respectively.

Conclusions

In this largest retrospective analysis to date we observed that Ca/Mg infusions significantly reduced all grade oxaliplatin-related neurotoxicity. Ca/Mg infusions did not affect the clinical efficacy of treatment.     

Four different regimens of farnesyltransferase inhibitor tipifarnib in older,untreated acute myeloid leukemia patients: North American Intergroup Phase II study SWOG S0432

We report on 348 patients ≥ 70 years (median age 78 years) with acute myeloid leukemia (>50% with secondary AML) randomized to receive either 600 mg or 300 mg of tipifarnib orally twice daily on days 1–21 or days 1–7 and 15–21, repeated every 28 days (4 treatment regimens). Responses were seen in all regimens, with overall response rate (CR + CRi + PR) highest (20%) among patients receiving tipifarnib 300 mg twice daily on days 1–21. Toxicities were acceptable. Unless predictors of response to tipifarnib are identified, further study as a single agent in this population is unwarranted.     

A first prospective population-based analysis investigating the actual practice of melanoma diagnosis, treatment and follow-up

Aim of the study: To describe the current management of patients diagnosed with cutaneous melanoma and melanoma in situ in Germany and assess for adherence with the existing German guideline in a first prospective population-based analysis.Methods: Prospective and longitudinal population-based study using online questionnaires. Registration by practitioners and hospitals was open for all patients diagnosed with melanoma between April and June 2008 in Germany. For data analysis, patients with melanoma stages 0-III (AJCC 2002) were included.Results: Data from 1081 patients registered by 106 different centres were available for analysis. Male patients were significantly older than female patients (61.4 years versus 55.8 years, p < 0.0001) and presented with thicker primary tumours (1.62 mm [median 0.9 mm] versus 1.48 mm [median 0.8 mm], p = 0.01). Excessive safety margin excisions were most often applied in melanoma in situ and in small centres. Insufficient excision margins (6.9%) were associated with head and neck localisation, geographical region and implementation of further staging procedures. Decision on sentinel lymph node biopsy complied with the German guideline in >85% of cases and was dependent on age and tumour localisation. Only 60% of patients received a complete lymph node dissection (CLND) after a positive SLNB, the rate of CLND was lowest in older patients. Adjuvant treatments were initiated in only 34% of patients formally qualifying for adjuvant treatment based on guideline recommendations. Approximately half of all staging procedures were done in no-risk/low-risk tumour patients.Conclusions: Management of melanoma in Germany did not show great dependency on centre size, geographical area or treating physician but rather on patient and tumour characteristics. The low rate of adjuvant treatment initiations reflects the need of treatment options in this patient group. Excessive initial staging procedures generate significant costs.     

Screening for EGFR mutations in lung cancer, a report from India

Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including the lung malignancy. Genetic modifications such as deletions, insertions and Single Nucleotide Polymorphisms in the tyrosine kinase (TK) domain of EGFR is a common feature observed in most lung cancers. Gefitinib and erlotinib are commonly available therapeutic drugs which act as specific inhibitors for the tyrosine kinase domain of EGFR and associated with EGFR mutations in exons 18-21. However the prevalence of mutation varies among ethnicity, grade, age and gender. This is the first report on the prevalence of EGFR mutation in non-small cell lung cancer patients using DNA obtained from samples such as biopsy/cytology/pleural fluid and Fine Needle Aspiration (FNA), across India. We have screened for 29 somatic mutations which span exons 18, 19, 20 and 21 of EGFR gene using Scorpion probe based ARMS-PCR technique. DNA from 220 NSCLC tissue samples were analyzed for EGFR mutations and mutations were detected in 51.8% of the study population. Among the mutant positive cases, the deletions in exon 19 (52%) and a missense mutation L858R in exon 21 (26%) were most predominant. There was a significant increase in overall mutations (p = 0.01) as a function of age, mutation in exons 19 and 21 together (p = 0.003), mutations in exons 18, 19 and 21 (p = 0.04) and mutations in exons 18 and 19 (p = 0.03) in females. Mutations did not seem to significantly correlate metastases or disease progression. Mutations in exons [19] and 21 together were significant in non-smokers compared to smokers (p = 0.01) using Mann-Whitney tests. The study suggests high prevalence of EGFR positivity in NSCLC in Indian sub-population and provides opportunities for targeted therapies for this group.     

Improvements in breast cancer survival over time,related to adjuvant treatment and node status

Background

There has been an increase in the use and effectiveness of adjuvant treatment for operable breast cancer and the aim of this study was to examine whether this has resulted in improved survival for all prognostic groups.

Methods

A retrospective study of 1517 patients with invasive breast cancer treated between 1980 and 2002 was carried out. The use of adjuvant treatment was compared between two time periods in patients based on nodal status, and survival was calculated by Kaplan–Meier life table analysis. Independent predictors for recurrence-free survival (RFS) were determined by Cox regression analysis.

Results

The use of adjuvant therapy increased for all prognostic groups. On multivariate analysis the use of radiotherapy and endocrine therapy was positively associated with RFS which was significant in the second time period. Outcome in node positive patients improved: five-year RFS from 59% to 76%, p < 0.01 and breast cancer specific survival (BCSS) from 70% to 83%, p < 0.01. However, there was no survival improvement in the larger group of node negative patients; BCSS 93% versus 95%, p = 0.99. Within the node negative group, patients with tumours ≥ 2 cm had an improved RFS from 80% to 88%, p = 0.02.

Conclusion

The increased use of adjuvant therapy was associated with an improved outcome in node positive patients. For node negative patients with good prognostic features the evidence of benefit was marginal.     

A multicentre dose-escalating study of cabazitaxel (XRP6258) in combination with capecitabine in patients with metastatic breast cancer progressing after anthracycline and taxane treatment: a phase I/II study

Background

Most patients with metastatic breast cancer (MBC) progress after chemotherapy. Cabazitaxel (XRP6258) is a new taxoid that is active in chemotherapy-resistant tumour cell lines. The objectives of this phase I/II study were to assess the maximum tolerated dose (MTD), safety profile, pharmacokinetics, and activity of cabazitaxel plus capecitabine in patients with MBC who had been previously treated with taxanes and anthracyclines.

Patients and methods

In part I, we used a 3 + 3 dose-escalation scheme to assess the MTD of intravenous cabazitaxel (day 1) with oral capecitabine twice daily (days 1-14) every 3 weeks. In part II, we evaluated the objective response rate (ORR) at the MTD.

Results

Thirty-three patients were enrolled and treated (15 in part I; 18 in part II). Cabazitaxel 20 mg/m² plus capecitabine 1000 mg/m² was the MTD. Pharmacokinetic analysis showed no apparent drug-drug interaction. In all patients, the main grade 3-4 toxicities were asthenia (n = 5), hand-foot syndrome (n = 5), neutropenia (n = 21), neutropenic infection (n = 1), and neutropenic colitis (n = 1). One patient had febrile neutropenia. Antitumour activity was observed at all dose-levels with two complete responses, five partial responses (PRs), and 20 disease stabilisations (seven unconfirmed PR). At the MTD, 21 patients were evaluable for efficacy. The ORR was 23.8% (95% CI: 8.2-47.2%). The median response duration was 3.1 months (95% CI: 2.1-8.4 months), with four of five lasting for more than 3 months. Median time to progression was 4.9 months.

Conclusions

Cabazitaxel combined with capecitabine is active, has a safety profile consistent with a taxane plus capecitabine combination and warrants further investigation in patients with MBC.     

CD56 expression is an independent prognostic factor for relapse in acute myeloid leukemia with t(8;21)

We investigated the significance of surface antigen expression for prognosis by focusing on a specific subtype, AML with t(8;21). The investigation included 144 patients with AML with t(8;21) in the JALSG AML97 study. AML with t(8;21) expressed CD19 (36%), CD34 (96%), and CD56 (65%) more frequently than did other subtypes of AML. CD19 expression had a significant favorable effect on CR (95.7% vs. 83.8%; P = 0.049). Univariate analysis showed that increased white blood cell (WBC) counts (WBC ≥ 20 × 10⁹/L), CD19 negativity, and CD56 positivity were critical adverse factors for relapse after CR; multivariate analysis revealed that WBC count and CD56 expression were independent adverse risk factors (HR 2.18; P = 0.045, HR 2.30; P = 0.011, respectively). We concluded that CD56 expression has a possible role in risk stratification for patients with AML with t(8;21).     

Repressive coping style: Relationships with depression, pain, and pain coping strategies in lung cancer out patients

Researchers have shown that coping style is related to pain and adjustment in people with chronic illness. This study was the first to examine how coping style related to pain, pain coping strategies, and depression in lung cancer outpatients. We conducted a comparative, secondary data analysis of 107 lung cancer patients (73% male, mean age 61.4 ± 10.43 years, 88% Caucasian). As in prior studies, we classified patients into four coping style groups based on Marlowe-Crowne Social Desirability Scale and trait anxiety scores. The coping style groups were low-anxious (n = 25); high-anxious (n = 31); defensive high-anxious (n = 21); and repressive (n = 30). Compared to other coping style groups, the repressive group reported statistically significant lower mean scores for pain quality, pain catastrophizing, and depression. Assessing coping style by measuring personal characteristics such as social desirability and trait anxiety may help clinicians to identify vulnerable individuals with lung cancer who may be candidates for early and timely intervention efforts to enhance adjustment to pain.     

Durable palliation of breast cancer chest wall recurrence with radiation therapy, hyperthermia, and chemotherapy

Background and purpose

Chest wall recurrences of breast cancer are a therapeutic challenge and durable local control is difficult to achieve. Our objective was to determine the local progression free survival (LPFS) and toxicity of thermochemoradiotherapy (ThChRT) for chest wall recurrence.

Methods

Twenty-seven patients received ThChRT for chest wall failure from 2/1995 to 6/2007 and make up this retrospective series. All received concurrent superficial hyperthermia twice weekly (median 8 sessions), chemotherapy (capecitabine in 21, vinorelbine in 2, and paclitaxel in 4), and radiation (median 45 Gy). Patients were followed up every 1.5-3 months and responses were graded with RECIST criteria and toxicities with the NCI CTC v4.0.

Results

Twenty-three (85%) patients were previously irradiated (median 60.4 Gy) and 22 (81%) patients received prior chemotherapy. Median follow-up was 11 months. Complete response (CR) was achieved in 16/20 (80%) of patients with follow-up data, and 1 year LPFS was 76%. Overall survival was 23 months for patients with CR, and 5.4 months in patients achieving a partial response (PR) (p = 0.01). Twenty-two patients experienced acute grade 1/2 treatment related toxicities, primarily moist desquamation. Two patients experienced 3rd degree burns; all resolved with conservative measures.

Conclusions

ThChRT offers durable palliation and prolonged LPFS with tolerable acute toxicity, especially if CR is achieved.     

A phase I dose-escalation study of MSC1992371A,an oral inhibitor of aurora and other kinases,in advanced hematologic malignancies

A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients with hematologic malignancies. Patients received escalating doses either on days 1–3 and 8–10 (n = 36) or on days 1–6 (n = 39) of a 21-day cycle. The maximum tolerated doses were 37 and 28 mg/m²/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses.     

Phase II study of preoperative chemoradiotherapy (CRT) with irinotecan plus S-1 in locally advanced rectal cancer

Background and purpose

The aim of this study is to evaluate the efficacy and safety of preoperative radiation therapy combined with S-1 and irinotecan (SI) in LARC.

Materials and methods

Patients were considered LARC if they had a T3/T4 lesion or node positive. Weekly doses of 40 mg/m² irinotecan were intravenously administered once per week during weeks 1-5 of radiotherapy. S-1 (70 mg/m²) was given from Monday to Friday in all weeks of radiotherapy. 3-D conformal radiotherapy was given at daily fractions of 1.8 Gy for 5 days for a total dose of 50.4 (45 + 5.4) Gy. Surgery was performed 4-6 weeks following the completion of chemoradiation.

Results

Between June 2006 and November 2007, 43 pts were enrolled. The stage was: cT3 24 patients, cT4 6 patients; 28 patients were cN+. Forty-one patients completed the chemoradiation and 42 patients underwent operation: a low anterior resection was performed in 36 patients, a total colectomy in 1 patient, and an abdominal perineal resection in 5 patients. T downstaging was observed in 50%; 23 N+ patients became N− (55%). The complete pathological response was observed in 9 patients (21%). The 3-year locoregional failure rate, distant failure rate, disease-free survival, and overall survival were 9.5%, 18.6%, 72.1%, and 94.3%, respectively. Only three patients experienced G3 diarrhea; one had G3 sepsis and two had septic shock. Hematological toxicity (G3-G4) was observed in five patients.

Conclusions

This study demonstrated the efficacy of preoperative CRT with S-1 and irinotecan with 21% of complete response. However, prompt recognition and management of infection is needed to use it in patients with locally advanced rectal cancer.     

Palliative brachytherapy with or without primary stent placement in patients with oesophageal cancer,a randomised phase III trial

Purpose

To investigate whether a combination of self-expanding metal stent (SEMS) and brachytherapy provided more rapid and prolonged effect on dysphagia without increased pain compared to brachytherapy alone in patients with incurable oesophageal cancer.

Methods

41 Patients were randomised to SEMS followed by brachytherapy, 8 Gy × 3 (n = 21) or brachytherapy alone, 8 Gy × 3 (n = 20). Change in dysphagia and pain three and seven weeks after randomisation (FU1 and FU2) was assessed by patient-reported outcome. Dysphagia, other symptoms and health-related quality of life were assessed every four weeks thereafter. The study was closed before the estimated patient-number was reached due to slow recruitment.

Results

Patients receiving SEMS followed by brachytherapy had significantly improved dysphagia at FU1 compared to patients receiving brachytherapy alone (n = 35). Difference in pain was not observed. At FU2, patients in both arms (n = 21) had less dysphagia. Four patients in the combined treatment arm experienced manageable complications, no complications occurred after brachytherapy alone.

Conclusion

For the relief of dysphagia, SEMS followed by brachytherapy is preferable and safe for patients in need of immediate alleviation, while brachytherapy with or without preceding SEMS provides relief within a few weeks after treatment.     

A multicenter phase II study to evaluate the efficacy and safety of gefitinib as first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations

This study was designed to prospectively evaluate the efficacy and safety of first-line gefitinib treatment in patients with advanced pulmonary adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations and to explore the molecular factors affecting the efficacy of gefitinib. Tumor tissue, derived from either the original tumor or the metastatic or recurrent site was taken from chemo-naïve pts with advanced (stage IIIB, IV, and recurrent) pulmonary adenocarcinoma. Tumor genomic DNA underwent direct sequencing for EGFR exons 18, 19, 20, and 21. Patients with EGFR mutations received 250 mg of gefitinib daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and tolerability. Out of 147 screened patients, 45 pts (31%) had EGFR mutations and received gefitinib. The most common EGFR mutations were in-frame exon 19 deletions (29 pts, 64%) and L858R point mutation in exon 21 (15 pts, 33%). One patient had atypical mutation of L861Q in exon 21. The ORR was 53.3% (95% CI, 38.6-67.9) and disease control rate (DCR) including stable disease was 86.7%. The median progression free survival (PFS) was 398 days and the median overall survival (OS) was 819 days. Treatment was well tolerated. Grade 3/4 adverse events (AEs) were reported by 6 patients and treatment-related Grade 3 AEs by 3 patients. There were no treatment-related Grade 4 AEs. Exploratory subgroup analysis according to the EGFR mutation subtypes was carried out. The ORR and DCR were higher in patients with exon 19 deletions than those with L858R (62.1% vs 33.3%; P = 0.0705 and 96.6% vs 66.7%; P = 0.0062, respectively). All 4 patients with progressive disease had a L858R mutation. No secondary resistant mutations such as T790M mutation or insertions in exon 20 were found in those patients. In addition, OS was significantly better in patients with exon 19 deletions than those with L858R (24-month OS rate was 72.1% vs 32.0%, P = 0.0148). Gefitinib as the first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations was effective and well tolerated. Subgroup analysis suggests that the benefit from gefitinib treatment was more prominent in patients with the exon 19 deletion mutations (ClinicalTrials.gov number, NCT00344773).     

Dosimetric predictor identification for radiation-induced liver disease after hypofractionated conformal radiotherapy for primary liver carcinoma patients with Child-Pugh Grade A cirrhosis

Purpose

Radiation-induced liver disease (RILD) is the most severe complication in liver cancer treatment. The aim of this study was to identify dosimetric predictors for RILD in primary liver carcinoma (PLC) patients with Child-Pugh Grade A cirrhosis after hypofractionated conformal radiotherapy (CRT).

Methods and materials

A total of 114 eligible patients (mean age 45 years old) were enrolled and treated. The mean gross tumor volume (GTV) was (378.3 ± 308.1) cm³. A median dose of 53 Gy was delivered to the PLC by hypofractionated CRT (three fractions/week) with a median fraction size of 4.6 Gy (range: 4-6 Gy).

Results

Patients were followed up for 1-79 months (median 19 months) after the completion of irradiation. RILD was diagnosed in nine (7.9%) patients. Univariate analyses revealed that GTV and the percentage of normal liver volume receiving more than 5-40 Gy irradiations (V_5-40) were related to the risk of developing RILD. Multivariate analyses demonstrated that only GTV and V₂₀ were independent predictors. Using V₂₀ as the predictor for RILD, the accuracy, sensitivity, and specificity was 76.3%, 88.9%, and 75.2%, respectively.

Conclusions

Our data suggest that V₂₀ is the unique significant dosimetric predictor for RILD risks in PLC patients with Child-Pugh Grade A cirrhosis after hypofractionated CRT.     

A phase I, dose-escalation study of pomalidomide (CC-4047) in combination with gemcitabine in metastatic pancreas cancer

Introduction

Pomalidomide is an investigational immunomodulating drug (IMiD®) that also inhibits angiogenesis and has direct anti-tumour effects. This phase I study was performed to identify the optimal dose of pomalidomide to be used in combination with gemcitabine in the treatment of patients with metastatic pancreatic cancer.

Methods

Eligible patients had histologically documented metastatic adenocarcinoma of the pancreas. No prior gemcitabine for metastatic disease or for primary treatment of locally advanced disease was allowed although prior radiation therapy with 5-flourouracil (5-FU) or gemcitabine as a radiosensitizer was allowed. All patients received gemcitabine 1000 mg/m² IV on days 1, 8 and 15 of a 28 day cycle. Pomalidomide was administered orally on days 1−21 at doses escalated from 2 to 10 mg daily. Patients were re-evaluated every 8 weeks; treatment continued until disease progression or intolerable toxicity occurred.

Results

Twenty-three patients were enrolled with a median age of 62 and Eastern Cooperative Oncology Group (ECOG) performance status 0 (87%) and 1 (13%). The maximum tolerated dose (MTD) was 10 mg/day on days 1−21. Neutropaenia was the most common grade 3/4 toxicity (38%); other grade 3/4 toxicity included deep vein thrombosis (DVT) (22%) and anaemia (9%). While efficacy was not a primary end-point of this study, 3 of 20 evaluable patients (15%) had partial responses and 10 patients (50%) had >50% decrease in CA 19-9 levels.

Conclusions

The combination of pomalidomide and gemcitabine was feasible and safe in most patients receiving first-line chemotherapy for metastatic pancreatic cancer. Neutropaenia, the dose-limiting toxicity, was brief and reversible. Intermittent dosing of pomalidomide allowed substantially higher doses than were previously reported with a continuous schedule. This combination merits further evaluation in the treatment of metastatic pancreatic cancer.     

A phase I study using bortezomib with weekly idarubicin for treatment of elderly patients with acute myeloid leukemia

We report the results of a phase I study with four dose levels of bortezomib in combination with idarubicin. Eligible patients were newly diagnosed with acute myeloid leukemia (AML) age ≥60 years, or any adult with relapsed AML. Bortezomib was given twice weekly at 0.8, 1.0, or 1.2 mg/m² with once weekly idarubicin 10 mg/m² for four weeks. Twenty patients were treated: 13 newly diagnosed (median age 68, range 61–83) and 7 relapsed (median age 58, range 40–77). Prior myelodysplastic syndrome (MDS) was documented in 10/13 (77%) newly diagnosed and 1/7 (14%) relapsed patients; the three newly diagnosed patients without prior MDS had dyspoietic morphology. Two dose-limiting toxicities occurred at the initial dose level (bortezomib 0.8 mg/m² and idarubicin 10 mg/m²); idarubicin was reduced to 8 mg/m² without observing subsequent dose-limiting toxicities. The maximum tolerated dose in this study was bortezomib 1.2 mg/m² and idarubicin 8 mg/m². Common adverse events included: neutropenic fever, infections, constitutional symptoms, and gastrointestinal symptoms. No subjects experienced neurotoxicity. Most patients demonstrated hematologic response as evidenced by decreased circulating blasts. Four patients (20%) achieved complete remission. There was one treatment-related death. The combination of bortezomib and idarubicin in this mostly poor-risk, older AML group was well tolerated and did not result in high mortality. This trial was registered at www.clinicaltrials.gov as #NCT00382954.     

Patterns of distant brain recurrences after radiosurgery alone for newly diagnosed brain metastases: Implications for salvage therapy

Introduction

Single modality radiosurgery (RS) is an established treatment option for patients with brain metastases (BM) with the aim of achieving optimal local control while avoiding toxicity from whole brain radiotherapy (WBRT). Published studies generally lack detailed data on distant brain recurrence (DBR) rates and characteristics. This study describes the patterns of DBR and consequences for salvage treatment in a group of patients treated with RS alone for 1–3 BM.

Materials and methods

Between 2002 and 2012, 443 patients were treated with RS alone in doses ranging 15–24 Gy in 1–3 fractions. Patient selection for RS was performed using triple dose gadolinium-enhanced MRI scans, obtained with slice distance of 2 mm (until 2008), 1.5 mm (2008–2012), and of 1 mm (from 2012). During follow-up, a DBR was observed in 147 patients, but in 20 of these patients (14%) these “new lesions” could retrospectively be seen on the planning MRI scan. These missed metastases had a median size of 2 mm, and in order to study real DBR patterns, these patients were excluded from analysis.

Results

Actuarial DBR rates at 6, 12 and 24 months in the remaining 423 patients were 21%, 41% and 54%, respectively, with a median time to DBR of 5.6 months. In 42% of DBR, a single new lesion was seen, in 70% there were ?3 new lesions. Median diameter of the DBR was 6 mm; 97% of lesions were ?30 mm. Salvage therapy was delivered in 82% of DBR patients, consisting of WBRT (46%), repeated RS (27%), or systemic treatment (9%). A RPA classification system (DBR-RPA), based on WHO performance status and interval between initial RS and diagnosis of DBR, was developed to estimate life expectancy after the development of DBR, which can be used to guide salvage therapy.

Conclusions

In this study of patients treated with RS alone, only 25% of treated patients needed salvage treatment for DBR, and ultimately only 18% of all patients underwent WBRT at any time during follow-up. A three-monthly MRI follow-up scheme identifies DBR at an early stage with respect to size and number of lesions, and most patients were asymptomatic at radiological diagnosis.     

Prospective,randomized, controlled,and open study in primarily inoperable,stage III non-small cell lung cancer (NSCLC) patients given sequential radiochemotherapy with or without epoetin alfa

Background and purpose

Induction chemotherapy is associated with anemia in non-small cell lung cancer (NSCLC) patients undergoing radiotherapy. This randomized, open-label study compared the effect of sequential radiochemotherapy (RCHT) versus RCHT + epoetin alfa (RCHT + EPO), with respect to 2-year overall survival (OS).

Material and methods

Patients ? 18 years received sequential RCHT; one arm also received EPO (chemotherapy day 1, when Hb < 12 g/dL). Kaplan–Meier analysis with log-rank test, and Cox-regression methods were performed.

Results

Of the 385 patients randomized (RCHT + EPO: n = 195; RCHT: n = 190), 78 (RCTH + EPO: 46 [23.6%]; RCHT: 32 [16.8%]) were anemic at baseline. Two-year OS was higher in RCHT + EPO-treated versus RCHT-treated (28.5% [95% CI: 22.2–35.1%] versus 20.6% [95% CI: 15.1–26.8%] [p = 0.2278]), and requirement for RBC transfusion was lower (24/195 [12.3%] versus 61/190 [32.1%]). In anemic (baseline) patients (post hoc analysis), median survival was shorter in RCTH-treated (212 days) versus RCHT + EPO-treated (343 days) (Hazard ratio = 1.62 [95% CI: 0.99–2.63], p = 0.0525). Adverse events were documented in 72.7% (RCHT + EPO: 75.0%; RCHT: 70.5%) patients, and thrombovascular events (TVEs) in 45 patients (RCHT + EPO: 16.7%; RCHT: 7.9%; p = 0.0099).

Conclusions

A statistically non-significant trend for 2-year OS was observed in a sub-group of EPO-treated NSCLC-patients with baseline anemia, although this trend was not maintained in the overall population with inoperable NSCLC.     

The prevalence and burden of symptoms amongst cancer patients attending palliative care in two African countries

Background

The majority of cancer presentations in Africa are advanced and incurable, with incidence of malignancies projected to increase significantly. Despite the African cancer burden, almost nothing is known about the symptomatology of malignant progressive disease. This study aimed to determine the symptom prevalence and burden amongst advanced cancer patients in two African countries.

Methods

The Memorial Symptom Assessment Schedule Short Form (MSAS-SF) was used to measure the 7-d period prevalence and associated burden of multidimensional symptoms amongst adult patients attending palliative care in South Africa and Uganda. Further demographic and clinical variables were collected.

Results

Of the 112 patients recruited, 22 (19.6%) had an underlying HIV diagnosis. The most common cancer primaries were breast (N = 24), cervix (N = 21) and lung (N = 14). The mean number of symptoms was 18 (SD = 6.6). The five most prevalent symptoms were pain (87.5%), lack of energy (77.7%), feeling sad (75.9%), feeling drowsy (72.3%) and worrying (69.6%). The five symptoms ranked as most severe were as follows: pain n = 26 (23.2%), sexual problems n = 24 (21.4%), weight loss n = 21 (18.8%), ‘I don’t look like myself’ n = 21 (18.8%) and lack of energy n = 20 (17.9%).

Discussion

Pain and psychological problems were four of the five most common symptoms, found in more than 3 out of 4 patients. Our sample’s reported mean number of symptoms was far higher than reported in other global studies. These data can inform the delivery of appropriate clinical care. The prevalence of multidimensional symptoms underlines the importance of holistic approaches to patient assessment and management, taking account of multiple and potentially interacting symptoms and locally appropriate intervention.