Multicentre phase I-II trial of capecitabine and oxaliplatin in combination with radiotherapy for unresectable pancreatic and biliary tract cancer: The CORGI-U study

Background and Purpose

In this multicentre phase I-II trial we evaluated the feasibility and efficacy of capecitabine and oxaliplatin followed by the combination of these two drugs with radiotherapy in patients with locally advanced pancreatic or biliary tract cancer.

Material and methods

Thirty-nine patients with inextirpable adenocarcinoma of the pancreas, gallbladder or extrahepatic bile ducts were included. Two cycles of XELOX (capecitabine 1000 mg/m² bid d1-14 + oxaliplatin 130 mg/m² d1, q3w) were followed by XELOX-RT (radiotherapy (50.4 Gy), combined with capecitabine 750-675 mg/m² bid every radiotherapy day and oxaliplatin 40-30 mg/m² once weekly). Primary end-points were tolerance (phase I) and objective response (phase II).

Results

The maximum tolerated doses of oxaliplatin and capecitabine to combine with irradiation were 30 mg/m² and 675 mg/m², respectively. Twenty-one percent (95% CI: 9-38%) of evaluable patients achieved partial response. Five patients went through surgery (three R0 resections). Two-year survival was 28%, and estimated local tumour control rate at 2 years was 72%. The most common grade 3-4 toxicity was nausea and vomiting.

Conclusions

XELOX-RT (30 mg/m² oxaliplatin/675 mg/m² capecitabine in combination with 50.4 Gy/28 fractions) was well tolerated and effective for locally advanced pancreatic and biliary tract cancer.     

Efficacy and safety of low-dose metronomic chemotherapy with capecitabine in heavily pretreated patients with metastatic breast cancer

Aim

Registered dose capecitabine monotherapy is active against metastatic breast cancer (MBC), but retrospective analyses indicate that lower doses may be as effective and better tolerated. This study was conducted to assess the safety and efficacy of metronomic capecitabine in heavily pretreated patients with MBC.

Patients and methods

In this phase II study 60 MBC patients received continuous metronomic capecitabine monotherapy (1500 mg once a day). Primary endpoint was clinical benefit rate, secondary end points were clinical benefit rates (CBRs), tumour response rates (RRs), overall survival (OS), time to progression (TTP), duration of response (DOR) and toxicity.

Results

Fifty eight assessable patients received two or more 28-day cycles of metronomic capecitabine. The CBR was 62%. Median DOR was 7 months. Median TTP and OS were 7 and 17 months, respectively. Two partial responses and 7 cases of stable disease were recorded in 13 patients who had previously received capecitabine intermittently (2000 mg/m²/day on days 1-14 every 21 days) as first- or subsequent-line treatment for MBC. Grade 3-4 adverse events were uncommon; haematologic toxicity was infrequent (5%) and consistently mild.

Conclusion

This regimen of metronomic capecitabine displayed good activity and excellent tolerability in MBC patients, including those who had previously received the drug at standard doses.     

Pre-operative bevacizumab, capecitabine, oxaliplatin and radiation among patients with locally advanced or low rectal cancer: a phase II trial

Background

To evaluate the safety and efficacy of pre-operative chemoradiation, using capecitabine, oxaliplatin and bevacizumab with standard doses of radiation, in patients with high-risk rectal cancer.

Methods

Patients with locally advanced or low rectal cancer were treated with capecitabine 825 mg/m² twice daily on days 1-14 and 22-35, oxaliplatin 50 mg/m² on days 1, 8, 22 and 29, bevacizumab 5 mg/kg on days 14, 1, 15 and 29, and radiation 50.4 Gy in 28 fractions including boost. Total mesorectal excision was performed 7-9 weeks after chemoradiation. The primary end-point was complete tumour regression (ypT0NX) by central review.

Findings

Forty-two evaluable patients were enrolled, and 38 proceeded to definitive surgery. Eighteen patients (43%) had clinical T4 tumours and/or N2 tumours. Mean relative dose intensity was >90% for all systemic agents, and 97% for radiation. Grade 3/4 diarrhoea occurred in 10 patients (24%) and pain in 4 patients (10%) pre-operatively, while grade 3/4 pain, fatigue and infection were each reported among 5 patients (13%) post-operatively. Re-operation due to complications occurred in 4 patients (11%). Complete tumour regression (ypT0) was seen in 9 patients (23.7%) of which two had N1 disease and the pathological complete response (pCR) rate (ypT0N0) was 18.4%. Central review changed pathologic stage in six cases (16%).

Interpretation

In this study, pre-operative bevacizumab added to oxaliplatin, capecitabine and radiation was safe and resulted in a promising tumour regression rate. Surgical complications were closely monitored and occurred with the expected frequency. Central pathology review should be considered for trials with pathologic response as the primary end-point.

Funding

British Columbia Cancer Agency, Hoffmann-La Roche Canada and Sanofi-Aventis.     

Unilateral radiotherapy for tonsil cancer: Potential dose distribution optimization with a simple two-field intensity-modulated radiation therapy beam arrangement

Background and purpose

To evaluate the feasibility and dosimetric optimization potential of a unilateral two-field intensity-modulated radiotherapy (IMRT) technique in the curative treatment of lateralized tonsil cancer.

Materials and methods

Six patients with lateralized tonsillar carcinoma were treated unilaterally with a two-field IMRT technique (oblique-anterior and oblique-posterior fields, with or without collimator and couch rotation). Alternative IMRT plans using seven non-opposed coplanar fields were compared with the two-field plans for each patient.

Results

Planning target volume (PTV) coverage was excellent with the two-field technique, using a relatively low number of monitor units (MU) (median, 441; range, 309-550). Dose constraints were respected for all organs at risk (OAR). Mean doses to contralateral parotid and submandibular glands were 3.9 and 17.7 Gy, respectively. Seven-field IMRT provided similar PTV coverage, with statistically significant better dose homogeneity and conformality. However, the mean delivered dose to the contralateral parotid (3.9 vs. 9.0 Gy, p = 0.001) as well as the mean number of MU (437 vs. 814, p = 0.002) and consequently machine time were lower with two-field IMRT.

Conclusions

Unilateral two-field IMRT is a simple and feasible technique providing excellent tumor coverage and optimal OAR sparing while reducing the number of MU and treatment time.     

Secondary radiation doses of intensity-modulated radiotherapy and proton beam therapy in patients with lung and liver cancer

Purpose

To compare the secondary radiation doses following intensity-modulated radiotherapy (IMRT) and proton beam therapy (PBT) in patients with lung and liver cancer.

Methods and materials

IMRT and PBT were planned for three lung cancer and three liver cancer patients. The treatment beams were delivered to phantoms and the corresponding secondary doses during irradiation were measured at various points 20-50 cm from the beam isocenter using ion chamber and CR-39 detectors for IMRT and PBT, respectively.

Results

The secondary dose per Gy (i.e., a treatment dose of 1 Gy) from PBT for lung and liver cancer, measured 20-50 cm from the isocenter, ranged from 0.17 to 0.086 mGy. The secondary dose per Gy from IMRT, however, ranged between 5.8 and 1.0 mGy, indicating that PBT is associated with a smaller dose of secondary radiation than IMRT. The internal neutron dose per Gy from PBT for lung and liver cancer, 20-50 cm from the isocenter, ranged from 0.03 to 0.008 mGy.

Conclusions

The secondary dose from PBT is less than or compatible to the secondary dose from conventional IMRT. The internal neutron dose generated by the interaction between protons and body material is generally much less than the external neutron dose from the treatment head.     

Single Arc Volumetric Modulated Arc Therapy of head and neck cancer

Background

The quality of Volumetric Modulated Arc Therapy (VMAT) plans is highly dependent on the performance of the optimization algorithm used. Recently new algorithms have become available which are capable of generating VMAT plans for Elekta accelerators. The VMAT algorithm in Pinnacle³® is named SmartArc and its capability to generate treatment plans for head and neck cancer was tested.

Methods

Twenty-five patients with oropharyngeal or hypopharyngeal carcinoma, previously treated with IMRT by means of Pinnacle³® and Elekta accelerators, were replanned with single arc VMAT. The VMAT planning objectives were to achieve clinical target coverage and sparing of the organs at risk (OAR). Comparison with the original clinically used IMRT was made by evaluating (1) dose-volume histograms (DVHs) for PTVs, (2) DVHs for OARs, (3) delivery time and monitor units (MU), and (4) treatment accuracy.

Results

Equivalent or superior target coverage and sparing of OARs were achieved with VMAT compared to IMRT. Volumes in the healthy tissues receiving between 17.3 Gy and 49.4 Gy were significantly reduced and the conformity (CI_95%) of the elective PTV was improved from 1.7 with IMRT to 1.6 with VMAT. Compared to step-and-shoot IMRT, VMAT reduced the number of MUs by 8.5% to 460 ± 63 MUs per fraction, and delivered on an Elekta Synergy accelerator, the treatment time was on average reduced by 35% to 241 ± 16 s. In Delta4® measurements of the VMAT treatments, 99.6 ± 0.5% of the detector points passed a 3 mm and 3% gamma criterion, identical to the results of IMRT.

Conclusions

The target coverages obtained in the IMRT and VMAT plans were found to be very similar. SmartArc generated single arc VMAT plans with equivalent or better target coverage and sparing of OARs compared to IMRT, while both delivery time and MUs were decreased. Very good dose accuracy results were obtained delivering the plans on an Elekta accelerator.     

Impact of target volumes and radiation technique on loco-regional control and survival for patients with unilateral cervical lymph node metastases from an unknown primary

Purpose

To compare the impact of an unilateral post-operative irradiation or a bilateral irradiation in terms of loco-regional control and survival in patients with cervical lymph node of squamous cell carcinoma from an unknown primary (CUP).

Methods and materials

Ninety five patients with epidermoid carcinoma involving unilateral cervical lymph nodes from an unknown primary were treated in two institutions from 1990 to 2007. Post-operative radiation therapy was delivered to one side of the neck in 59 cases, to both sides of the neck in 36 cases. There were 11 women and 84 men ranging in age from 38 to 80 years (median 59 years). Neck dissection was performed in 79 patients while 16 patients underwent single lymph node sampling only.

Results

After a median follow-up of 3.3 years, the nodal relapse rate was 34% after unilateral neck irradiation and 25% after bilateral radiotherapy (p = 0.21). Six contralateral lymph node relapses occurred after unilateral irradiation (10%). The 5-year overall survival rate of the entire group was 24%. The 5-year OS rates were 22% after unilateral irradiation and 23%, after bilateral radiotherapy (p = 0.944). The occult primary occurred in 12% after unilateral irradiation and 6% after bilateral radiotherapy. The radiation technique (3D-CRT or IMRT vs. 2D: p = 0.026) was prognostic on loco-regional control. Independent prognostic determinants on overall survival were the WHO status (p = 0.013) and the radiation technique (2D vs. 3D-CRT or IMRT; p = 0.029). There was no difference in loco-regional control (p = 0.639) and no difference in survival (p = 0.493) when chemotherapy was associated.

Conclusions

Retrospective comparisons between bilateral and unilateral neck radiotherapies did not show differences in terms of loco-regional control and survival. However, patient’s local regional control and survival are significantly improved after 3D-CRT or IMRT.     

A study of middle ear function in the treatment of nasopharyngeal carcinoma with IMRT technique

Purpose

This study evaluates the difference in damage to middle ear function with CRT and IMRT techniques in the treatment of nasopharyngeal carcinoma (NPC). We explore the isthmus of the Eustachian tube (ET) as the key anatomic site for the prevention of radiation-induced otitis media with effusion.

Methods and materials

Eighty-two patients with NPC were divided into two groups: 40 patients treated with CRT and 42 patients treated with IMRT. The difference between dosage over the middle ear cavity and the isthmus of the ET was evaluated in both CRT group and IMRT group. All patients underwent hearing tests including pure tone audiometry and impedance audiometry before and after RT.

Results

The dosage difference to the middle ear cavity and isthmus between these two groups was statistically significant (p < 0.05). The difference in hearing test results between these two groups was also statistically significant (p < 0.05). If we limited the dose to the middle ear cavity under 34 Gy and the dose to the isthmus under 53 Gy with IMRT, we may decrease radiation-induced OME even with the larger 2.25 Gy fraction size.

Conclusions

IMRT may have better protected the middle ear function compared with the CRT technique, even with larger fraction sizes than for the conventional CRT technique.     

TS expression predicts postoperative recurrence in adenocarcinoma of the lung

Background

Not all patients with lung cancer require postoperative adjuvant chemotherapy after a complete resection. However, no useful markers for either selecting appropriate candidates or for predicting clinical recurrence exist.

Methods

Tumor specimens were collected from 183 consecutive patients who underwent a complete resection for lung adenocarcinoma from 2003 to 2007 in our department. We analyzed the thymidylate synthase (TS) and dihydrofolate reductase (DHFR) expressions in the primary lung adenocarcinoma by immunohistochemisty.

Results

The strong expression of TS and DHFR was identified in 39 (21.3%) and 120 (65.6%) patients, respectively. The strong TS expression was identified in 11 (39.3%) of 28 patients and 28 (18.1%) of 155 patients in patients with and without recurrence, respectively (p = 0.012). The strong DHFR expression was also identified in 23 (82.1%) and 97 (62.6%) of the patients with and without recurrence, respectively (p = 0.045). Logistic regression models indicated the strong TS expression to be an independent factor for tumor recurrence. The strong TS and DHFR expression was associated with a poorer disease-free survival (DFS) according to the survival analysis. A multivariate analysis demonstrated the strong TS expression to be independently associated with an increased risk for poor DFS.

Conclusions

The strong TS expression may be a useful marker for predicting postoperative recurrence in patients with lung adenocarcinoma following surgery.     

Compensatory enlargement of the liver after treatment of hepatocellular carcinoma with carbon ion radiotherapy - Relation to prognosis and liver function

Background and purpose

To examine whether liver volume changes affect prognosis and hepatic function in patients treated with carbon ion radiotherapy (CIRT) for hepatocellular carcinoma (HCC).

Material and methods

Between April 1995 and March 2003, among the cases treated with CIRT, 43 patients with HCC limited to the right hepatic lobe were considered eligible for the study. The left lateral segment was defined as the non-irradiated region. Liver volume was measured using contrast CT at 0, 3, 6, and 12 months after CIRT. We examined serum albumin, prothrombin activity, and total bilirubin level as hepatic functional reserve.

Results

After CIRT, the non-irradiated region showed significant enlargement, and enlarged volume of this region 3 months after CIRT ?50 cm³ was a prognostic factor. The 5-year overall survival rates were 48.9% in the larger enlargement group (enlarged volume of non-irradiated region 3 months after CIRT ?50 cm³) and 29.4% in the smaller enlargement group (as above, <50 cm³). The larger enlargement group showed better hepatic functional reserve than the smaller enlargement group 12 months after CIRT.

Conclusions

This study suggests that compensatory enlargement in the non-irradiated liver after CIRT contributes to the improvement of prognosis.     

The effect of delineation method and observer variability on bladder dose-volume histograms for prostate intensity modulated radiotherapy

Purpose

To quantify the effect of delineation method on bladder DVH, observer variability (OV) and contouring time for prostate IMRT plans.

Materials and methods

Planning CT scans and IMRT plans of 30 prostate cancer patients were anonymized. For 20 patients, 1 observer delineated the bladder using 9 methods. The effect of delineation method on the DVH curve, discrete dose levels and delineation time was quantified. For the 10 remaining CTs, 6 observers delineated bladder wall using 4 methods. Observer-based volume variation and intraclass correlation coefficient (ICC) were used to describe the dosimetric effects of OV.

Results

Manual delineation of the bladder wall (BW_m) was significantly slower than any other method (mean: 20 min vs. ?13 min) and the dosimetric effect of OV was significantly larger (V70 Gy ICC: 0.78 vs. 0.98). Only volumes created using a 2.5 mm contraction from the outer surface, and a method providing a consistent wall volume, showed no notable dosimetric differences from BW_m in both absolute and relative volume.

Conclusions

Automatic contractions from the outer surface provide quicker, more reproducible and reasonably accurate substitutes for BW_m. The widespread use of automatic contractions to create a bladder wall volume would assist in the consistent application of IMRT dose constraints and the interpretation of reported dose.     

Tumour growth rates and RECIST criteria in early drug development

Purpose

The evaluation of treatment efficacy with RECIST criteria does not take into account tumour growth dynamics. We notably investigated the impact of the pre-treatment tumour growth rate (GR) on the evaluation of treatment response.

Patients and methods

Seventy-six patients included in phase I clinical trials had scanographic evaluations before and after starting an experimental treatment. The GR was calculated for the pre-treatment period and for the experimental period (i.e. during the new treatment). Tumour response was evaluated per protocol at week 12 and at week 24 of the experimental period according to RECIST criteria. We studied the relation between pre-treatment and experimental GRs and RECIST tumour response.

Results

On average the tumour GR was decreased by 40% during the experimental period; compared to the pretreatment period (p = 0.03). An increased growth rate (acceleration of GR during experimental treatment compared to pretreatment) was observed in 20 (38%) of the 53 patients considered as non-progressive at week 12 according to RECIST. Conversely a decreased GR was observed in 12 out of 23 (53%) patients classified as progressive according to RECIST. The variation in the GR between the pre-treatment and experimental period was not significantly correlated with response evaluated according to RECIST at week 12 or at week 24 (p = 0.45 and 0.44, respectively).

Conclusions

RECIST evaluation of tumour response depends on the natural history of the tumours and poorly measures the impact of treatment on the kinetics of tumour growth. Integrating pre-treatment GR evaluations could substantially improve the assessment of treatment efficacy in drug development.     

Hypoxia imaging with [F-18] FMISO-PET in head and neck cancer: Potential for guiding intensity modulated radiation therapy in overcoming hypoxia-induced treatment resistance

Background and purpose

Positron emission tomography (PET) imaging with [F-18] fluoromisonidazole (FMISO) has been validated as a hypoxic tracer [1] and [2]. Head and neck cancer exhibits hypoxia, inducing aggressive biologic traits that impart resistance to treatment. Delivery of modestly higher radiation doses to tumors with stable areas of chronic hypoxia can improve tumor control [3]. Advanced radiation treatment planning (RTP) and delivery techniques such as intensity modulated radiation therapy (IMRT) can deliver higher doses to a small volume without increasing morbidity. We investigated the utility of co-registered FMISO-PET and CT images to develop clinically feasible RTPs with higher tumor control probabilities (TCP).

Materials and methods

FMISO-PET images were used to determine hypoxic sub-volumes for boost planning. Example plans were generated for 10 of the patients in the study who exhibited significant hypoxia. We created an IMRT plan for each patient with a simultaneous integrated boost (SIB) to the hypoxic sub-volumes. We also varied the boost for two patients.

Result

A significant (mean 17%, median 15%) improvement in TCP is predicted when the modest additional boost dose to the hypoxic sub-volume is included.

Conclusion

Combined FMISO-PET imaging and IMRT planning permit delivery of higher doses to hypoxic regions, increasing the predicted TCP (mean 17%) without increasing expected complications.     

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.     

Volumetric modulated arc therapy versus conventional intensity modulated radiation therapy for stereotactic spine radiotherapy: A planning study and early clinical data

Background and purpose

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc®, RA) and conventional intensity-modulated radiotherapy (IMRT).

Materials and methods

RA and IMRT plans to deliver a fraction of 16 Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body (n = 3), while group 2 had PTVs encompassing the entire vertebra (n = 4). Finally, RA delivery parameters in four patients were assessed.

Results

Both techniques delivered 16 Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V_{10-partial cord} for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2-3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4 min.

Conclusions

Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.     

Current technological clinical practice in breast radiotherapy; results of a survey in EORTC-Radiation Oncology Group affiliated institutions

Purpose

To evaluate the current technological clinical practice of radiation therapy of the breast in institutions participating in the EORTC-Radiation Oncology Group (EORTC-ROG).

Materials and methods

A survey was conducted between August 2008 and January 2009 on behalf of the Breast Working Party within the EORTC-ROG. The questionnaire comprised 32 questions on 4 main topics: fractionation schedules, treatment planning methods, volume definitions and position verification procedures.

Results

Sixty-eight institutions out of 16 countries responded (a response rate of 47%). The standard fraction dose was generally 2 Gy for both breast and boost treatment, although a 2.67 Gy boost fraction dose is routinely given in British institutions. The main boost modality was electrons in 55%, photons in 47% and brachytherapy in 3% of the institutions (equal use of photon and electron irradiation in 5% of the institutions). All institutions used CT-based treatment planning. Wide variations are seen in the definition of the breast and boost target volumes, with margins around the resection cavity, ranging from 0 to 30 mm. Inverse planned IMRT is available in 27% and breath-hold techniques in 19% of the institutions. The number of patients treated with IMRT and breath-hold varied per institution. Electronic portal imaging for patient set-up is used by 92% of the institutions.

Conclusions

This survey provides insight in the current practice of radiation technology used in the treatment of breast cancer among institutions participating in EORTC-ROG clinical trials.     

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.     

Radical prostatectomy vs. intensity-modulated radiation therapy in the management of localized prostate adenocarcinoma

Background and purpose

To determine whether radical prostatectomy (RP) or intensity-modulated radiation therapy (IMRT) to ?72 Gy, plus hormonal therapy if indicated, results in improved biochemical disease-free survival (BDFS) in localized prostate adenocarcinoma.

Materials and methods

Between 1997 and 2005, a consecutive sample of 556 patients who underwent RP (n = 204) or IMRT (n = 352) at two referral centers was analyzed. The patients were stratified into prognostic groups based on clinical stage, Gleason score, and pretreatment prostate-specific antigen (PSA). The outcome measure was BDFS.

Results

IMRT patients had more advanced disease at baseline (p < .001). There was no difference in five-year BDFS rates between RP and IMRT in the favorable (92.8% vs. 85.3%, p = .20) or intermediate prognosis (86.7% vs. 82.2%, p = .46) subsets. A difference favoring IMRT plus hormonal therapy was seen in the poor prognosis (38.4% vs. 62.2%, p < .001) subset. Within the entire cohort, after adjustment for confounding variables, Gleason score (p < .001) and clinical stage (p < .001) predicted BDFS, but treatment modality (p = .06) did not. Within the poor prognosis subset, treatment modality (p = .006) predicted BDFS.

Conclusions

BDFS is similar between RP and IMRT for patients with a favorable or intermediate prognosis. Patients with a poor prognosis display higher BDFS when treated with IMRT to ?72 Gy plus hormonal therapy.