Low-dose radiotherapy and concurrent FOLFIRI-bevacizumab: a Phase II study.

AIMS: Low-dose radiation therapy (LDRT) can increase biological efficacy of chemotherapy. This Phase II trial evaluates LDRT plus FOLFIRI-bevacizumab (FOLFIRI-B) in metastatic colorectal cancer. PRIMARY OBJECTIVE: raising the clinical complete response rate from 5 to 25%. SECONDARY OBJECTIVES: toxicity, progression-free survival. Patients underwent 12 FOLFIRI-B cycles plus two daily LDRT fractions (20 cGy/6 h interval) on each cycle. Statistical analysis was planned on 18 patients. RESULTS: Results on 18 patients are reported. Specifically considering irradiated sites: 15/18 patients had a partial (11/18) or complete (4/18) response. Among 11 partial responders, three became a pathological CR after surgery. Grade 3-4 toxicity was recorded in two patients (11.1%). At median follow-up of 30 months (range: 8-50), 7/18 patients progressed in irradiated sites. CONCLUSION: Seven out of 18 patients (38.9%) had clinical or pathological CR in lesions treated with LDRT. Further studies on this newer treatment modality seem justified.

Safety and Efficacy of a First-Line Chemotherapy Tailored by G8 Score in Elderly Metastatic or Locally Advanced Gastric and Gastro-Esophageal Cancer Patients: A Real-World Analysis.

Introduction: Gastric (GC) and gastro-esophageal cancer (GEC) are common neoplasms in the elderly. However, in clinical practice, the correct strategy for elderly patients who might benefit from chemotherapy (CT) is unknown. Prospective data are still poor. In this context, we performed a retrospective analysis of GC patients aged ≥75 years and treated at our institutions. Material and Methods: We retrospectively analyzed 90 patients with confirmed metastatic GC or GEC, treated with an upfront CT. Inclusion criteria were patients aged ≥75 years, PS 0−2, normal bone marrow/liver/renal function and no major comorbidities. All patients received a G8 score, and some patients with G8 ≤14 received a comprehensive geriatric assessment (CGA). The primary goal was to perform a safety evaluation based on the incidence of adverse events (AE), and the secondary goal was to determine the efficacy (PFS and OS). The chi-square test and the Kaplan−Meier method were used to estimate the outcomes. The statistical significance level was set at p < 0.05. Results: Toxicity rates were quite low: G1/G2 (51.1%) and G3/G4 (25.5%). No toxic deaths were reported. The median PFS was 6.21 months and the median OS 11 months. The G8 score and PS ECOG significantly influenced both PFS and OS. A statistically significant correlation among G8, weight loss, hypoalbuminemia and risk of G3/G4 adverse events was also found. Conclusion: Our research on selected elderly patients did not detect broad differences of efficacy and tolerability compared to a young population. Our study, although retrospective and small-sized, showed that G8 score might be an accurate tool to identify elderly GC/GEC patients who could be safely treated with CT, further recognizing patients who could receive a doublet CT and who may require a single agent chemotherapy or a baseline dose reduction.

Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study.

BACKGROUND: An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy. MATERIAL AND METHODS: A Phase II study was designed and clinical stage T3-T4 and/ or N ≥ 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehan's design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria. RESULTS: Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12-55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18-63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 1-2 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively. CONCLUSION. An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).

Capecitabine based postoperative accelerated chemoradiation of pancreatic carcinoma. A dose-escalation study.

UNLABELLED: The objective of this study was to evaluate the safety of escalating up to 55 Gy within five weeks, the dose of external beam radiotherapy to the previous tumor site concurrently with a fixed daily dose of capecitabine, in patients with resected pancreatic cancer. MATERIAL AND METHODS: Patients with resected pancreatic carcinoma were eligible for this study. Capecitabine was administered at a daily dose of 1600 mg/m (2). Regional lymph nodes received a total radiation dose of 45 Gy with 1.8 Gy per fractions. The starting radiation dose to the tumor bed was 50.0 Gy (2.0 Gy/fraction, 25 fractions). Escalation was achieved up to a total dose of 55.0 Gy by increasing the fraction size by 0.2 Gy (2.2 Gy/fraction), while keeping the duration of radiotherapy to five weeks (25 fractions). A concomitant boost technique was used. Dose limiting toxicity (DLT) was defined as any grade>3 hematologic toxicity, grade>2 liver, renal, neurologic, gastrointestinal, or skin toxicity, by RTOG criteria, or any toxicity producing prolonged (> 10 days) radiotherapy interruption. RESULTS AND DISCUSSION: Twelve patients entered the study (median age: 64 years). In the first cohort (six patients), no patient experienced DLT. Similarly in the second cohort, no DLT occurred. All 12 patients completed the planned regimen of therapy. Nine patients experienced grade 1-2 nausea and/or vomiting. Grade 2 hematological toxicity occurred in four patients. The results of our study indicate that a total radiation dose up to 55.0 Gy/5 weeks can be safely administered to the tumor bed, concurrently with capecitabine (1600 mg/m (2)) in patients with resected pancreatic carcinoma.

Post-Operative Accelerated-Hypofractionated Chemoradiation With Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost in Glioblastoma: A Phase I Study (ISIDE-BT-2).

BACKGROUND: Glioblastoma Multiforme (GBM) is the most common primary brain cancer and one of the most lethal tumors. Theoretically, modern radiotherapy (RT) techniques allow dose-escalation due to the reduced irradiation of healthy tissues. This study aimed to define the adjuvant maximum tolerated dose (MTD) using volumetric modulated arc RT with simultaneous integrated boost (VMAT-SIB) plus standard dose temozolomide (TMZ) in GBM. METHODS: A Phase I clinical trial was performed in operated GBM patients using VMAT-SIB technique with progressively increased total dose. RT was delivered in 25 fractions (5 weeks) to two planning target volumes (PTVs) defined by adding a 5-mm margin to the clinical target volumes (CTVs). The CTV1 was the tumor bed plus the MRI enhancing residual lesion with 10-mm margin. The CTV2 was the CTV1 plus 20-mm margin. Only PTV1 dose was escalated (planned dose levels: 72.5, 75, 77.5, 80, 82.5, 85 Gy), while PTV2 dose remained unchanged (45 Gy/1.8 Gy). Concurrent and sequential TMZ was prescribed according to the EORTC/NCIC protocol. Dose-limiting toxicities (DLTs) were defined as any G ≥ 3 non-hematological acute toxicity or any G ≥ 4 acute hematological toxicities (RTOG scale) or any G ≥ 2 late toxicities (RTOG-EORTC scale). RESULTS: Thirty-seven patients (M/F: 21/16; median age: 59 years; median follow-up: 12 months) were enrolled and treated as follows: 6 patients (72.5 Gy), 10 patients (75 Gy), 10 patients (77.5 Gy), 9 patients (80 Gy), 2 patients (82.5 Gy), and 0 patients (85 Gy). Eleven patients (29.7%) had G1-2 acute neurological toxicity, while 3 patients (8.1%) showed G ≥ 3 acute neurological toxicities at 77.5 Gy, 80 Gy, and 82.5 Gy levels, respectively. Since two DLTs (G3 neurological: 1 patient and G5 hematological toxicity: 1 patient) were observed at 82.5 Gy level, the trial was closed and the 80 Gy dose-level was defined as the MTD. Two asymptomatic histologically proven radionecrosis were recorded. CONCLUSIONS: According to the results of this Phase I trial, 80 Gy in 25 fractions accelerated hypofractionated RT is the MTD using VMAT-SIB plus standard dose TMZ in resected GBM.

Results of a phase II study of Short-course Accelerated Radiation Therapy (SHARON) for multiple brain metastases.

OBJECTIVES: To assess the effectiveness of a SHort-course Accelerated RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. MATERIALS AND METHODS: A phase II clinical trial was designed. Eligibility criteria included patients with at least 3 brain metastases or metastatic disease in >3 organ systems, and Eastern Cooperative Oncology Group performance status of ≤3. Fifty patients were treated with whole brain radiotherapy at 18 Gy (4.5 Gy per fraction) in 2 days with a twice daily fractionation. The primary endpoint was the assessment of efficacy in terms of overall survival. RESULTS: Characteristics of the 50 enrolled patients were: male/female: 24/26; median age: 65 years (range, 45 to 80 y). Eastern Cooperative Oncology Group performance status was <3 in 42 patients (84%). Nineteen patients (38%) were considered to have recursive partitioning analysis class 3 disease. Grade 1-2 acute neurological (46%) and skin (24%) toxicities were recorded. Three patients (6%) experienced neurological grade 3 acute toxicity. With a median follow-up time of 6 months (range, 1 to 18 mo) 2 skin grade 1 late toxicities has been observed. Seventeen of 27 symptomatic patients showed an improvement or resolution of baseline symptoms (overall palliative response rate: 63.0%; 95% confidence interval, 36.6%-82.4%).Two-month overall survival was 86% (median survival time=7 mo). CONCLUSIONS: Short-course accelerated whole brain radiotherapy of 18 Gy in twice daily fractions for 2 consecutive days is tolerated and effective in terms of symptom relief and median survival time. These results justify a phase III comparison against the standard-of-care in this patient population (30 Gy in 10 fractions).

FOLFIRI-bevacizumab and concurrent low-dose radiotherapy in metastatic colorectal cancer: preliminary results of a phase I-II study.

BACKGROUND: To evaluate the effectiveness of low-dose radiation therapy (LDRT) and FOLFIRI-bevacizumab (FOLFIRI-B) combination in metastatic colorectal cancer. METHODS: The primary objective of the study is to raise the clinical complete response (CR) rate from 5% to 25%. Secondary objectives include toxicity and progression-free survival. Patients underwent 12 FOLFIRI-B cycles plus two daily LDRT (20 cGy/6-hour interval) on the first and second days of each cycle. RESULTS: CR and toxicity of 10 patients are reported. Considering irradiated sites, 10/10 patients had clinical partial response (PR) (7/10) or CR (3/10). Three clinical PR patients subsequently underwent surgery and reported a pathological CR in the irradiated sites. Grade 3-4 toxicities rate was 30%. With a median follow-up of 29 months (range: 12-49 months), 2/10 progression of disease in irradiated sites and 3/5 in non-irradiated sites were observed. CONCLUSIONS: The very high response rate requires urgent verification in a larger patient series.

Volumetric intensity modulated arc therapy for stereotactic body radiosurgery in oligometastatic breast and gynecological cancers: feasibility and clinical results.

In the present study, the preliminary results of the first stereotactic body radiosurgery (SRS) experience with volumetric intensity modulated arc therapy (VMAT) in oligometastatic breast and recurrent gynecological tumors (OBRGT) are reported in terms of feasibility, toxicity and efficacy. Patients were treated in a head-first supine treatment position on a customized body frame immobilization shell. SRS-VMAT treatment plans were optimized using the ERGO++ treatment planning system. Response assessment was performed 8-12 weeks after treatment by morphologic imaging modalities, or if feasible, also by functional imaging. Thirty-six lesions in 24 consecutive patients (median age, 63 years; range, 40-81) were treated: 13.9% had primary or metastatic lung lesions, 30.5% had liver metastases, 36.1% had bone lesions, 16.7% had lymph node metastases and 2.8% had a primary vulvar melanoma. The median dose was 18 Gy (BED2 Gy, α/ß: 10=50.4 Gy), the minimal dose was 12 Gy (BED2 Gy, α/ß: 10=26.4 Gy) and the maximal dose was 28 Gy (BED2 Gy, α/ß: 10=106.4 Gy). Seven patients (29.2%) experienced acute toxicity, which however was grade 2 in only 1 case. Moreover, only 3 patients (12.5%) developed late toxicity of which only 1 was grade 2. Objective response rate was 77.7% including 16 lesions achieving complete response (44.4%) and 12 lesions achieving partial response (33.3%). The median duration of follow-up was 15.5 months (range, 6-50). Recurrence/progression within the SRS-VMAT treated field was observed in 6 patients (total lesions=7) with a 2-year inside SRS-VMAT field disease control expressed on a per lesion basis of 69%. Recurrence/progression of disease outside the SRS-VMAT field was documented in 15 patients; the 2-year outside SRS-VMAT field metastasis­free survival, expressed on a per patient basis, was 35%. Death due to disease was documented in 6 patients and the 2-year overall survival was 58%. Although the maximum tolerated dose was not reached, SRS-VMAT resulted in positive early clinical results in terms of tumor response, local control rate and toxicity.

Radiotherapy and concurrent metronomic chemotherapy in hormone-refractory prostate carcinoma: a Phase I study.

AIM: To determine the maximum tolerated dose of hypofractionated radiotherapy (HFRT) plus concurrent metronomic chemotherapy in patients with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: A Phase I clinical trial was performed with cohorts of three to six patients per group. Eligible patients had HRPC without distant metastases. The radiotherapy dose was escalated in a stepwise fashion as follows: 60, 65, and 70 Gy at levels 1, 2, and 3, respectively (25 fractions: levels 1-2, and 26 fractions: level 3). RESULTS: Nine patients were enrolled. The radiotherapy dose was escalated from 60 to 70 Gy without any dose-limiting toxicity. The most common grade 1/2 toxicities were hematuria, dysuria, diarrhea and rectal-perirectal pain. The overall objective response rate was 9/9 (100%) (95% CI=66.4%-100%). The median time-to-progression was 19 months. CONCLUSION: In the challenging setting of HRPC, HFRT up to 70 Gy with concurrent metronomic chemotherapy was well-tolerated and yielded encouraging disease control.

Hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost after radical prostatectomy: preliminary results of a phase II trial.

AIM: To report the acute toxicity of a hypofractionated regimen of intensity-modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) to the pelvic nodes and the prostatic bed after radical prostatectomy. PATIENTS AND METHODS: Patients with prostate adenocarcinoma at high risk of relapse after radical prostatectomy or with biochemical relapse were deemed eligible for study. SIB-IMRT was prescribed to the whole pelvis (45-Gy delivered in 1.8-Gy fractions) and the prostatic bed [62.5 Gy, 2.5-Gy fractions, Equivalent Dose in 2-Gy fraction (EQD2)=68.75 Gy, α/ß=3]. Acute toxicity was recorded and graded according to Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Forty-nine patients were enrolled. No cases of grade ≥ 3 acute toxicity were recorded. Grade 2 acute genitourinary and gastrointestinal toxicity was observed in 9.6% and 29.7% of patients, respectively. CONCLUSION: After radical prostatectomy, hypofractionated high-dose SIB-IMRT enables for reduction of the overall treatment time, with an acute toxicity profile which compares favourably with that of conventionally fractionated high-dose three-dimensional conformal radiotherapy (3D-CRT).

Incidence and management of noncancer pain in cancer patients referred to a radiotherapy center.

OBJECTIVES: The incidence of noncancer pain (NCP) in cancer patients is unknown. An analysis of incidence, severity, impact on quality of life (QoL), and appropriateness of NCP treatment in a cohort of cancer patients referred to a radiotherapy center is reported. MATERIALS AND METHODS: Pain was scored from 0 (absence) to 3 (severe) and the adequacy of analgesic therapy was evaluated according to International Guidelines. Correlation between Pain Management Index and World Health Organization Analgesic Ladder was used to analyze the appropriateness of NCP treatment. In addition, pain was differentiated according to its origin and types and a comparison was performed between cancer pain (CP) and NCP. RESULTS: A total of 903 patients were eligible and 865 (95.8%) were considered evaluable. Three hundred ninety-eight patients (46.0%) had pain. CP and NCP pain incidence was 11.2% and 34.8%, respectively. Pain intensity was higher in patients with CP versus NCP (P=0.021). A neuropathic pain lower incidence (P=0.024) in NCP versus CP was recorded. Moreover, NCP was more inadequately treated than CP (P<0.001). QoL was significantly lower in patients with NCP when compared with patients without pain (P<0.001). In addition, QoL of patients with CP was significantly lower than QoL of patients with NCP (P<0.001). DISCUSSION: In a cancer patients' population referred to a radiotherapy center, the NCP incidence was higher than the CP incidence and NCP intensity was only slightly lower than CP. NCP was significantly pharmacologically undertreated and it was related to a decline in QoL.

Extracranial radiosurgery with volumetric modulated arc therapy: Feasibility evaluation of a phase I trial.

The aim of this study was to report early clinical experience in stereotactic body radiosurgery (SBRS) delivered using volumetric intensity modulated arc therapy (VMAT) in patients with primary or metastatic tumors in various extra-cranial body sites. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, metastatic), and sequentially assigned to a particular dose level. Technical feasibility and dosimetric results were investigated. The acute toxicity, tumor response and early local control were also studied. In total, 25 lesions in 20 consecutive patients (male/female, 11/9; median age, 67 years; age range, 47-86 years) were treated. Of these 25 lesions, 4 were primary or metastatic lung tumors, 6 were liver metastases, 8 were bone metastases and 7 were nodal metastases. The dose-volume constraints for organs at risk (OARs) were observed in 19 patients using a single-arc technique. Only in one patient were two arcs required. The treatment was performed without interruption or any other technical issues. The prescribed dose ranged from 12-26 Gy to the planning target volume (PTV). Delivery time ranged from 4 min to 9 min and 13 sec (median, 6 min and 6 sec). No incidence of grade 2-4 acute toxicity was recorded. The overall response rate was 48% (95% confidence interval (CI), 24.2-70.2) based on computed tomography (CT)/magnetic resonance imaging (MRI) and 89% (95% CI, 58.6-98.7) based on the positron emission tomography (PET) scan. SBRS delivered by means of VMAT allowed the required target coverage to be achieved while remaining within the normal tissue dose-volume constraints in the 20 consecutive patients. VMAT-SBRS resulted in adequate technical feasibility; the maximum tolerable dose has not yet been reached in any study arm.

A phase I study of short-course accelerated whole brain radiation therapy for multiple brain metastases.

PURPOSE: To define the maximum tolerated dose (MTD) of a SHort-course Accelerated whole brain RadiatiON therapy (SHARON) in the treatment of patients with multiple brain metastases. METHODS AND MATERIALS: A phase 1 trial in 4 dose-escalation steps was designed: 12 Gy (3 Gy per fraction), 14 Gy (3.5 Gy per fraction), 16 Gy (4 Gy per fraction), and 18 Gy (4.5 Gy per fraction). Eligibility criteria included patients with unfavorable recursive partitioning analysis (RPA) class>or=2 with at least 3 brain metastases or metastatic disease in more than 3 organ systems, and Eastern Cooperative Oncology Group (ECOG) performance status≤3. Treatment was delivered in 2 days with twice-daily fractionation. Patients were treated in cohorts of 6-12 to define the MTD. The dose-limiting toxicity (DLT) was defined as any acute toxicity≥grade 3, according to the Radiation Therapy Oncology Group scale. Information on the status of the main neurologic symptoms and quality of life were recorded. RESULTS: Characteristics of the 49 enrolled patients were as follows: male/female, 30/19; median age, 66 years (range, 23-83 years). ECOG performance status was <3 in 46 patients (94%). Fourteen patients (29%) were considered to be in recursive partitioning analysis (RPA) class 3. Grade 1-2 acute neurologic (26.4%) and skin (18.3%) toxicities were recorded. Only 1 patient experienced DLT (neurologic grade 3 acute toxicity). With a median follow-up time of 5 months (range, 1-23 months), no late toxicities have been observed. Three weeks after treatment, 16 of 21 symptomatic patients showed an improvement or resolution of presenting symptoms (overall symptom response rate, 76.2%; confidence interval 0.95: 60.3-95.9%). CONCLUSIONS: Short-course accelerated radiation therapy in twice-daily fractions for 2 consecutive days is tolerated up to a total dose of 18 Gy. A phase 2 study has been planned to evaluate the efficacy on overall survival, symptom control, and quality of life indices.

Short-course accelerated radiotherapy in palliative treatment of advanced pelvic malignancies: a phase I study.

PURPOSE: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. METHODS AND MATERIALS: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of ≤ 3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). RESULTS: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). CONCLUSIONS: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

Feasibility study of moderately accelerated intensity-modulated radiotherapy plus concurrent weekly cisplatin after induction chemotherapy in locally advanced head-and neck cancer.

PURPOSE: To evaluate the feasibility and efficacy of moderately accelerated intensity-modulated radiation therapy (IMRT) along with weekly cisplatin, after induction chemotherapy, in patients with locally advanced unresectable head and neck cancer (HNC). METHODS AND MATERIALS: Patients with Stage III or IV locally advanced HNC, without progressive disease after three courses of induction chemotherapy, received concurrent chemo-IMRT (weekly cisplatin 30 mg/m(2) plus simultaneous integrated boost IMRT). A total of 67.5 Gy in 30 fractions were delivered to primary tumor and involved nodes, 60 Gy in 30 fractions to high-risk nodal areas, and 55.5 Gy in 30 fractions to low-risk nodal areas. RESULTS: In all, 36 patients (median age, 56 years) with International Union Against Cancer (UICC) Stage III (n = 5) and IV (n = 31) were included. Of the 36 patients, 17 had received CF (cisplatin and 5-fluorouracil (CF) and 19 had received docetaxel cisplatin and 5-fluorouracil (DCF). During concurrent chemoradiation, 11 of 36 patients (30.5%) experienced Grade III mucositis (CF, 47%; DCF, 15%; p < 0.04). Grade III pharyngeal-esophageal toxicity was observed in 5 of 19 patients (26.3%; CF, 0.0%; DCF, 26.3%; p = 0.02). Two patients died of complications (5.5%). After chemoradiation, the complete response rate was 63.8%. Two-year local control was 88.7%. Two-year progression free survival and overall survival were 74.5% and 60.9%, respectively. CONCLUSIONS: In our experience, a moderately accelerated chemo-IMRT was feasible after induction chemotherapy. However, a noteworthy early death rate of 5.5% was observed. Intensive supportive care strategies should be defined to better manage radiation-induced toxic effects. Longer follow-up is required to determine the incidence of late radiation toxicities and tumor control rates.

Multiple tumor marker elevation in androgen ablation-refractory prostate cancer with long-term response to metronomic chemotherapy: a case report.

Outcomes in hormone-refractory prostate cancer are very poor. The time from progression to death is only 12-19 months. We present the case of a 69-year-old man with hormone-refractory prostate cancer and bone metastases treated with metronomic chemotherapy (cyclophosphamide based). He had had a colon adenocarcinoma ten years before. The atypical features of this case were an unusually long-lasting response to metronomic chemotherapy and an increase in serum levels of some non-prostate-specific tumor markers (CEA and CA 19-9) that was not related to a relapse of colon cancer. We hypothesize a potential role of hypoxia inducing CA 19-9 and CEA expression in tumor cells, which may predict the development of progressive resistance to antiangiogenic therapies.