Epirubicin and ifosfamide in relapsed or refractory small cell lung cancer patients

Introduction

In small cell lung cancer (SCLC), despite the high response rates induced by platinum-based first line chemotherapies, relapse happens in 85% of the first-line responding tumors. Since 1992 we used a combination of epirubicin and ifosfamide (EI) as a non-cross-resistant regimen in relapsed or refractory SCLC. With the topotecan approval in second line treatment, this combination has been moved from the second line to the third line setting.

Methods

Patients presenting with a relapsed or refractory, histologically proven, SCLC were considered for this combination associating ifosfamide 3 g/m² day 1-2 with uroprotection using mesna, and epirubicin 90 mg/m² day 1 given every four weeks until progression or unacceptable toxicity.

Results

Seventy patients were accrued between September 1992 and August 2010 (seven women). Median age was 56 years. Performance Status was 0, 1, 2 and 3 for 16 (23%), 25 (35%), 20 (29%) and 9 (13%) patients respectively. Proportion of refractory, resistant and sensitive tumors was 20, 21 and 59% respectively. Median time from first line chemotherapy until progression was 90 days (range 5-1720 days). Forty-four patients were treated in second line setting whereas the 26 others have had received two lines at time of accrual. A total of 203 cycles were delivered (median 2 cycles, range: 1-6). Fifteen patients (21.4%) achieved an objective response (including one complete), and 10% had a stable disease. Median overall survival was 3.9 months (95% confidence interval: 3.3-5.1). Overall NCI-CTC grade 3 and 4 toxicity was mainly hematological: neutropenia (71% of the patients, febrile neutropenia 9.4% of the cycles), thrombocytopenia (23%), and anemia (22%). In univariate analysis, previous anthracyclines treatment was associated with a trend towards shorter survival (median overall survival 3.9 versus 4.6 months, p = 0.12). In multivariate analysis, only a high serum NSE level and presence of brain metastases were independent prognostic variables.

Conclusion

The EI combination is an active regimen in relapsed or refractory SCLC. The trend towards a greater activity of this regimen in patients not pretreated using anthracyclines suggests that class of agents should be tested in SCLC relapsing after the etoposide-platinum standard regimen.     

Three-dimensional conformal radiation therapy for squamous cell carcinoma of the esophagus: A prospective phase I/II study

Purpose

A prospective phase I-II study was conducted to determine the tolerance and local control rate of three-dimensional conformal radiotherapy (3-DCRT) for esophageal squamous cell carcinoma (SCC).

Methods and materials

Thirty patients underwent 3-DCRT for thoracic esophageal SCC. PTV1 composed of a 1.2-1.5 cm margin lateral around GTV and 3.0 cm margin superior/inferior of GTV. PTV2 encompassed GTV with a margin of 0.5-0.7 cm. The dose for PTV1 was 50 Gy in 2 Gy daily fractions; PTV2 received a boost of 16 Gy in 2 Gy daily fractions to a total dose of 66 Gy.

Results

Median follow-up time was 18 months. The most common acute toxicity was esophagitis in 63% of patients with RTOG grades 1-2, and in 3% with grade 3. RTOG grades 1-2 radiation pneumonitis developed in 27% of patients. One patient developed pulmonary fibrosis RTOG grade 2 and another patient experienced grade 3 pulmonary fibrosis. Two patients developed mild esophageal stricture requiring dilatation. Two-year overall survival, local disease progression-free rate, and distant metastasis-free rate were 69%, 36% and 56%, respectively.

Conclusions

Although 3-DCRT to 66 Gy for esophageal SCC was well tolerated, the local control was disappointing. The result supports the use of chemoradiation as the standard care for esophageal SCC.     

Duration of prior gefitinib treatment predicts survival potential in patients with lung adenocarcinoma receiving subsequent erlotinib

Purpose

We investigated survival potential in patients receiving erlotinib after failure of gefitinib, focusing on response and time to progression (TTP) with gefitinib.

Methods

We retrospectively reviewed lung adenocarcinoma patients who received erlotinib after experiencing progression with gefitinib. Our primary objective was to evaluate the prognostic significance of erlotinib therapy.

Results

A total 42 lung adenocarcinoma patients were included in this study. Overall disease control rate was 59.5% (partial response [PR], 2.4%; stable disease [SD], 57.1%). Median overall survival was 7.1 months, and median progression-free survival was 3.4 months. The number of patients who achieved PR and non-PR (SD+ progressive disease [PD]) with gefitinib were 22 (52%) and 20 (48%), respectively. Patients with PR for gefitinib showed significantly longer survival times than those with non-PR (9.2 vs. 4.7 months; p = 0.014). In particular, among PR patients, those with TTP <12 months on gefitinib showed significantly longer survival times than those with TTP ≥12 months (10.3 vs. 6.4 months; p = 0.04).

Conclusions

Erlotinib may exert survival benefit for lung adenocarcinoma patients with less than 12 months of TTP of prior gefitinib who achieved PR for gefitinib.     

Platinum-based doublet chemotherapy in pre-treated malignant pleural mesothelioma (MPM) patients: a mono-institutional experience

Background

The major clinical problems of MPM management are the short duration of response and the early relapse. Currently, after the first-line standard pemetrexed/platinum combination there is not a defined regimen for the second line treatment of MPM, and the clinical benefits in fit patients are uncertain. We analyzed the feasibility of gemcitabine/platinum chemotherapy in pretreated MPM patients.

Methods

Eligible patients should have relapsed after first-line chemotherapy with pemetrexed plus cisplatin (24%) or carboplatin (76%); 53% of the patients had previously received trimodality treatment, 18% neoadjuvant chemotherapy followed by pleurectomy/decortication, 29% were inoperable. Patients had to have PS = 0-2, adequate organ function, measurable disease.Chemotherapy was gemcitabine 1000 mg/m² days 1, 8 associated to the alternative platinum compound respect to 1st line, i.e. cisplatin 75 mg/m² or carboplatin AUC 5 day 1 every 3 weeks, for 3-6 cycles. Baseline staging and reassessment after cycles 3 and 6 were performed with CT-scan.

Results

Since 2006 17 relapsed MPM patients were referred to our centre. Patients were 12 males and 5 females; median age: 61 years (range 47-74); histology: 12 epithelial, 4 sarcomatoid and 1 biphasic. PS 1-2 (15:2).The combination of gemcitabine with carboplatin/cisplatin was administered as second line treatment in 13 (76%) patients, as third line in 4 (24%) patients. Two patients were lost to follow-up without re-evaluation, therefore radiologic and clinical response was assessable in 15 (88%) patients. Among evaluable patients 10 (67%) showed stable disease and 5 (33%) progressive disease. Symptoms improved in 8 (53%) cases. In the intent-to-treat population median survival was 28 weeks (range 13-168) and median time-to-treatment failure 15 weeks (range 3-75).Toxicity profile showed 2 (13%) grade 4 and 6 (40%) grade 3 thrombocytopenia, 4 (27%) grade 3 leucopenia, 3 (20%) grade 3 anaemia and 6 (40%) of grade 3 neutropenia. Grade 3 non haematological toxicities were nausea (14%) and asthenia (21%).

Conclusion

Gemcitabine-platinum regimens are able to control symptoms and disease progression with a modest toxicity profile. The present results from a small series of patients should be confirmed by a prospective trial in a larger cohort of patients.     

Reverse resistance to radiation in KYSE-150R esophageal carcinoma cell after epidermal growth factor receptor signal pathway inhibition by cetuximab

Background and purpose

The purpose of our study is to examine the capacity of cetuximab to reverse radiation resistance and investigate molecular mechanisms in human radiation-resistant esophageal carcinoma cell line KYSE-150R.

Materials and methods

The radioresistant cell line KYSE-150R was established by using fractionated irradiation (FIR). The KYSE-150R cell line was exposed to radiation, treatment with cetuximab, and combined treatment. Cell cycle distribution and apoptosis were analyzed using flow cytometry. Radiation survival was analyzed using clonogenic assays. RT² profiler™ PCR array was performed to analyze EGF/PDGF signaling pathway genes.

Results

The established esophageal carcinoma cell line KYSE-150R showed higher radioresistance than parental cell line. Cetuximab could reverse the radiation resistance of KYSE-150R cells. Cell cycle analysis showed that combination with radiation and cetuximab resulted in the accumulation of cells in G1 and G2/M phases, with the reduction of cells within the S phase. Cetuximab enhanced the apoptosis induced by radiation. RT² profiler™ array showed that some intracellular signaling genes deriving from EGF/PDGF signaling pathway regulated by cetuximab.

Conclusions

Irradiation combined with EGFR blocked by cetuximab may reverse the resistance to radiation in radioresistant esophageal carcinoma cell. The mechanisms may include cell cycle perturbation and enhancement of radiation-induced apoptosis. Further studies are needed to evaluate the role of cetuximab in combination with radiotherapy in the management of esophageal carcinoma.     

Prophylactic cranial irradiation in patients with small-cell lung cancer: the experience at the Institute of Oncology Ljubljana

Background

Prophylactic cranial irradiation (PCI) has been used in patients with small-cell lung cancer (SCLC) to reduce the incidence of brain metastases (BM) and thus increase overall survival. The aim of this retrospective study was to analyze the characteristics of patients with SCLC referred to the Institute of Oncology Ljubljana, their eligibility for PCI, patterns of dissemination, and survival.

Patients and methods

Medical charts of 357 patients with SCLC, referred to the Institute of Oncology Ljubljana between January 2004 and December 2006, were reviewed to determine characteristics of patients chosen for PCI. The following data were collected: age, gender, performance status (PS), extent of the disease, smoking status, type of primary treatment with outcome, haematological and biochemical parameters, PCI use, and finally brain metastases (BM) status at diagnoses and after treatment.

Results

PCI was performed in 24 (6.7%) of all patients. Six (25%) patients developed brain metastases after they were treated with PCI. Brain was the only site of metastases in 4 patients, two progressed to multiple organs. Median overall survival of patients with PCI was 21.9 months, without PCI 12.13 months (p = 0.004). From the collected data there were good prognostic factors: age under 65 years, limited disease (LD), performance status, normal levels of lactate dehydrogenase (LDH) and normal levels of C-reactive protein levels (CRP). Other prognostic factors did not show statistical significant values.

Conclusions

Survival of patients with LD, who have had PCI, was significantly better than those who had not. We decided to perform PCI in patients with LD, in those with complete or near complete response, and those with good performance status (≥ 80). We did not use PCI in extended disease (ED). The reason for that shall be addressed in the future. Doses for PCI were not uniform, therefore more standard approach should be considered.     

Stereotactic body radiation therapy for lung metastases

Introduction

Stereotactic body radiation therapy (SBRT) has an emerging role in patients affected with pulmonary metastases. Purpose of this study was to evaluate efficacy and tolerability of SBRT in a cohort of patients treated between 2003 and 2009 at our institution.

Methods

A total of 61 patients with oligometastatic lung tumors (single pulmonary nodules in 73.7%) were included in the study. SBRT was performed with a stereotactic body frame and a 3D-conformal technique. Fifty-one patients received 26 Gy in 1 fraction, 22 a dose of 45 Gy in 3 fractions and 3 a dose of 36 Gy in 4 fractions. Primary tumor was lung cancer in 45.7% of patients, colorectal cancer in 21.3% and a variety of other origins in 33%. The primary endpoint was local control, secondary endpoints were survival and toxicity.

Results

After a median follow-up interval of 20.4 months, local control rates at 2 and 3 years were 89% and 83.5%, overall survival 66.5% and 52.5%, cancer-specific survival 75.4% and 67%, progression-free survival 32.4% and 22.3%. Tumor volume was significantly associated to survival, with highest rates in patients with single small tumors. Median survival time was 42.8 months, while median progression-free survival time was 11.9 months. Toxicity profiles were good, with just one case of grade III toxicity (pneumonitis).

Conclusion

This study shows that SBRT is an effective and safe local treatment option for patients with lung metastases. Definitive results are strictly correlated to clinical selection of patients.     

Oncovascular surgery

Background

Surgical resection remains the cornerstone for the curative treatment of oncological disease. When a tumour mass encases a critical arterial or venous structure, successful symptom relief and long-term oncological control may be achieved through careful preoperative planning within a multi-disciplinary team incorporating oncological and vascular specialists. To highlight the strategic issues pertaining to the vascular management of these patients, this review addresses the principles in planning oncovascular surgery, namely where cancer resection necessitates concurrent ligation or reconstruction of a major vascular structure.

Design

A multiple electronic health database search was performed, including Medline, Embase, and Scopus.

Results

The published outcomes for different malignancies suggest that survival is dependent upon complete clearance of the primary pathology and tumour biology rather than vascular-related complications.

Conlcusion

Major vessel involvement of a tumour mass should not necessarily be considered a barrier to en bloc resection and hence curative surgery. Radical surgical resection may offer the only chance for cure or palliation for these patients. Detailed preoperative planning within an extended multi-disciplinary team that includes vascular specialists is essential for these complex patients.     

Robotic system-based fractionated stereotactic radiotherapy in locally recurrent nasopharyngeal carcinoma

Purpose

We reviewed survival, local control, and toxicity in patients with locally recurrent nasopharyngeal carcinoma (NPC) who had been treated with fractionated stereotactic radiotherapy (FSRT).

Materials and methods

Between June 2002 and March 2008, we retrospectively reviewed 35 patients with locally recurrent NPC treated using FSRT with CyberKnife. Gross tumor volumes ranged from 2.6 to 64.0 ml (median, 7.9 ml). Radiation doses were prescribed at the isodose line (75-84% of the maximum dose; median, 80%). The prescribed dose of FSRT ranged from 24 to 45 Gy (median, 33 Gy) in three or five fractions.

Results

The overall survival (OS) rate, local failure-free survival (LFFS) rate, and disease progression-free survival (DPFS) rate at 5 years were 60%, 79%, and 74%, respectively. Twenty-three patients achieved complete response after FSRT. Only T stage at recurrence was an independent prognostic factor for OS and DPFS. Five patients exhibited severe late toxicity (Grade 4 or 5).

Conclusions

With regard to OS and LFFS, our study provided favorable outcomes. The incidence of severe late toxicities was acceptable in our study. FSRT would be considered as the alternative treatment of choice in re-irradiation for locally recurrent NPC.     

Total quality culture in radiotherapy departments across Ontario

Purpose

To investigate the prevalence of total quality culture (TQC) within radiation therapy (RT) departments across Ontario, Canada.

Methods

A prospective quantitative survey was distributed within RT departments across Ontario, Canada using the Miller Consulting Group Quality Culture survey.

Findings

Ninety percent of managers (9/10) and 50% of employees (261/519) participated. There was concordance between managers and staff that overall RT departments exhibit a work culture that somewhat resembles TQC. Both groups scored 55% of the categories as somewhat agree with TQC and 9% of categories as no TQC. There was discordance in views for 36% of the categories, where managers scored a higher prevalence of TQC compared to their therapists. Larger RT departments (>50 employees) had more prevalence of discrepancy between group scores.

Conclusions

This is the first study to report on the prevalence of TQC within RT departments. Strategies designed for on-going continuous improvement will benefit staff, RT managers, continuity of patient care and patient safety within RT departments.     

Phase II trial of the combination of carboplatin and irinotecan in elderly patients with small-cell lung cancer

Aim

The aim of the present phase II study was to assess the antitumour activity and safety of the combination of irinotecan and carboplatin in elderly patients with small-cell lung cancer (SCLC).

Material and methods

Patients with previously untreated SCLC were eligible if they had a performance status of 0-2, were 70 years or older, and had adequate organ function. Patients were treated with carboplatin at an area under the plasma concentration versus time curve of 5 min/ml on day 1 and with irinotecan at 50 mg/m² on days 1 and 8 every 3 weeks.

Results

Thirty patients (26 men and 4 women; median age, 76 years; age range, 70-86 years) were enrolled. Eight patients had limited disease (LD) and 22 patients had extensive disease (ED). The overall response rate was 83.3% (95% confidence interval: 65.3-94.4%). Response rates did not differ significantly between patients with LD (87.5%) and those with ED (81.8%; p = 0.71). The median survival time was 14 months overall and was significantly longer in patients with LD (26 months) than in patients with ED (11 months; p = 0.025). The median progression free survival time was 6 months overall and was significantly longer in patients with LD (12 months) than in patients with ED (6 months; p = 0.016). Grade 3-4 toxicities included neutropenia in 83% of patients, thrombocytopenia in 47%, anaemia in 60%, infection in 23%, and diarrhoea in 20%. There were no treatment-related deaths.

Conclusions

This chemotherapy is safe and effective for elderly patients with SCLC.     

Interstitial brachytherapy using stereotactic implanted (125)iodine seeds for recurrent medulloblastoma

Aims

To evaluate the efficacy of interstitial brachytherapy using ¹²⁵iodine (¹²⁵I) seeds for the treatment of recurrent multimodal treated medulloblastoma.

Materials and methods

Between September 1989 and August 2009, 12 patients (female:male = 3:9, median age 19 years, range 7-55 years) with 23 recurrent medulloblastomas underwent interstitial brachytherapy using ¹²⁵I seeds. Before brachytherapy, all patients underwent microsurgical resection; six patients underwent a combined adjuvant treatment consisting of craniospinal irradiation and chemotherapy; three received craniospinal irradiation alone and two received chemotherapy alone. One patient was treated by surgery alone. The median tumour volume was 4.9 ml (range 0.4-44.2 ml), the median tumour surface dose 50 Gy (range 32-50 Gy) and the median implantation time 42 days (range 42-90 days). A median follow-up of 26 months was available (range 5-116 months).

Results

After brachytherapy, nine of 23 tumours (39%) presented a complete remission, nine (39%) a partial remission and five (22%) stable disease on magnetic resonance images. The neurological status improved in six patients and remained unchanged in four. Two patients deteriorated: one developed spinal metastasis and another a treatment-related adverse radiation effect. Ten patients died due to disseminated disease despite local tumour control. The median survival after treatment was 15 months (range 5-68 months).

Conclusions

Our results show a good response of recurrent medulloblastoma after interstitial brachytherapy. High rates of tumour remission were yielded with low rates of treatment-related morbidity. Thus, ¹²⁵I seed brachytherapy should be considered as a treatment option for recurrent medulloblastoma.     

Impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer submitted to extended lymph node dissection

Purpose

This study was designed to establish whether the number of lymph nodes removed has an effect on prognosis in patients with node-negative gastric cancer.

Patients and Methods

We retrospectively analysed data of 114 consecutive patients who underwent gastrectomy and extended lymph node dissection for node-negative adenocarcinoma of the stomach between 2000 and 2005. Standard survival methods and restricted cubic spline multivariable Cox regression models were applied.

Results

Median age was 63 years and 67 patients out of 114 (59%) were males. Median number of dissected LNs was 22 (range 2-73). Median follow-up was 76 months. Patients who had ≤15 nodes removed had significantly worse distant disease-free survival, disease-free survival and overall survival at multivariable analysis than other patients. The results did not change when pT1 and pT2-3 cancer patients were analysed separately. The risk of distant metastases decreased as the number of dissected lymph nodes increased (>15).

Conclusions

More extended lymph node resection offered survival benefit even in the subgroup of patients with early stage disease. Lymphadenectomy involving more than 15 lymph nodes should be performed for the treatment of node-negative gastric cancer.

Synopsis

The impact on survival of the number of lymph nodes removed in patients with node-negative gastric cancer has not been established. This study suggests that more extended lymph node resection offers protection, as patients who had ≤15 nodes removed had significantly worse disease-free survival and overall survival at multivariate analysis than patients in whom >15 nodes were removed.     

Definitive chemoradiation for oesophageal cancer--a standard of care in patients with non-metastatic oesophageal cancer

Aims

A retrospective analysis was carried out of 291 cases of oesophageal cancer treated with definitive chemoradiotherapy (dCRT) at a single UK cancer centre between 1995 and 2009. Our protocol consisted of two cycles of neoadjuvant platinum-based chemotherapy followed by two further cycles given concurrently with 50 Gy of external beam radiotherapy delivered in 25 fractions over 5 weeks.

Materials and methods

Demographic, patient and outcome data were recorded prospectively through an electronic health record and retrospectively analysed, using appropriate statistical tools.

Results

Data on 266 patients were available for analysis. The median age was 66.6 years, 53% were adenocarcinomas. dCRT was used instead of surgery because of age/co-morbidity in 44% and disease extent in 39%. Ninety-three per cent of patients completed treatment according to protocol. Grade 3 and 4 toxicities were seen in 42 and 7%, respectively. Median survival was 20.6 months; 2, 3 and 5 year survival rates were 43.6, 32.9 and 19.5%, respectively. Advanced disease was associated with a worse outcome. Shorter disease length was associated with a better median survival, but some patients with disease >10 cm had long-term disease control. The effect of other patient- and disease-related factors was also analysed.

Conclusion

We present data showing that dCRT is well tolerated and should be considered as an alternative to surgery for all patients with locally advanced oesophageal cancer, not only those with co-morbidity. Furthermore, the benefits of dCRT are not confined to carcinomas with squamous histology.     

A phase II study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in relapsed small cell lung cancer

Introduction

We previously reported data on the safety, tolerability, and recommended phase II dose of obatoclax mesylate in conjunction with topotecan in patients with advanced solid tumor malignancies. Preliminary efficacy data suggested activity in patients with recurrent small cell lung cancer (SCLC). Based on these data, we performed a phase II study of obatoclax mesylate plus topotecan in patients with relapsed SCLC to assess efficacy.

Methods

This was an open-label, single-arm, phase II extension of obatoclax mesylate plus topotecan in patients with relapsed SCLC. Obatoclax mesylate was given intravenously (IV) at a dose of 14 mg/m² on days 1 and 3 with IV topotecan at 1.25 mg/m² on days 1-5 of an every 3-week cycle. The primary end-point of this study was overall response rate.

Results

Nine patients with recurrent SCLC were enrolled into the first stage of the study. Patients received a median of 2 cycles of treatment. All patients were evaluable for the primary end-point of overall response. There were no partial or complete responses. Five patients (56%) had stable disease. The remaining four patients (44%) developed progressive disease. The most common grade 3 or 4 adverse events included thrombocytopenia (22%), anemia (11%), neutropenia (11%), and ataxia (11%).

Conclusion

Obatoclax mesylate added to topotecan does not exceed the historic response rate seen with topotecan alone in patients with relapsed SCLC following the first-line platinum-based therapy.     

Incidence of isolated regional recurrence after definitive (chemo-) radiotherapy for head and neck squamous cell carcinoma

Objective

To evaluate the incidence and localization of regional recurrences after definitive (chemo-) radiotherapy for head and neck squamous cell carcinoma (HNSCC).

Methods

From May 1987 to March 2008, 368 patients with advanced HNSCC were irradiated to 66-80.5 Gray in 6-7 weeks, with (37%) or without (63%) concomitant chemotherapy (Cisplatinum 100 mg/m²) every 3 weeks. No planned neck dissections were performed. Data on clinical outcome were retrospectively reviewed, location of the original nodal disease and the regional recurrence was indicated on imaging and correlated with radiation dose.

Results

Mean follow-up was 34 months (range: 50 days-216 months). Three-year overall survival and disease-specific survival were 55% and 62%, respectively. Loco-regional, local and regional controls were 58%, 65%, and 80%, respectively. Forty-one patients (11.1%) relapsed in the neck, but only 11 patients (2.99%) developed a true isolated regional recurrence, 6 of whom could be successfully salvaged by surgery. Only 2 patients (0.54%) developed an isolated recurrence in the electively treated nodal levels.

Conclusion

Isolated nodal recurrences are uncommon and recurrences in the electively treated neck are extremely uncommon.     

Long-term results of concurrent radiotherapy and UFT in patients with locally advanced pancreatic cancer

Background

Definition and treatment options for locally advanced non-resectable pancreatic cancer (LAPC) vary. Treatment options range from palliative chemotherapy to chemoradiotherapy (CRT). Several studies have shown that a number of patients become resectable after complementary treatment prior to surgery.

Methods

From 2001 to 2005, 63 consecutive patients with unresectable LAPC received CRT. CRT was given at a dose of 50 Gy/27 fractions, combined with UFT (300 mg/m²/day) and folinic acid. Re-evaluation of resectability was planned 4-6 weeks after completion of CRT.

Results

Fifty-eight patients completed all 27 treatment fractions. Toxicity was generally mild, with 18 patients experiencing CTCAE grade 3 or worse acute reactions. One patient died following a treatment-related infection. Two patients developed grade 4 upper GI bleeding. Median survival was 10.6 (8-13) months. Eleven patients underwent resection, leading to a resection rate of 17%, and a median survival of 46 (23-nr) months. All 11 patients had a R0 resection. Median survival for the patients not resected was 8.8 (8-12) months.

Conclusion

CRT with 50 Gy combined with UFT, is a well-tolerated and effective treatment for patients with LAPC. R0 resection was possible in 17% leading to a long median survival of 46 months in resected patients.     

Concurrent doxorubicin and radiotherapy for anaplastic thyroid cancer: A critical re-evaluation including uniform pathologic review

Background and purpose

Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy. The potential for pathologic misclassification complicates interpretation of published data. One standard treatment option for locoregionally advanced disease is weekly low-dose doxorubicin with concurrent radiation therapy, and was previously developed at our institution. We evaluated our more recent experience with this approach, which included pathologic confirmation of all cases.

Materials and methods

A retrospective review was performed on patients identified through the Memorial Sloan-Kettering Cancer Center (MSKCC) Cancer Database. Inclusion criteria: pathologically confirmed ATC; locoregional disease encompassable within a radiation portal; treatment with curative intent at MSKCC with planned weekly doxorubicin (10 mg/m²) and concurrent radiation. Principle outcomes assessed were locoregional progression-free survival (LR-PFS) and overall survival (OS).

Results

Thirty-seven patients were included. Median radiotherapy dose was 57.6 Gy, and was ?50 Gy in 29 (78%), administered through hyperfractionated or once-daily schedules. One-year outcomes were LR-PFS, 45%; OS, 28%.

Conclusion

The prognosis of patients with ATC remains grim and our current results appear inferior to those reported previously by our institution. More accurate histologic diagnoses and patient selection in the present series compared to the prior one may be responsible in part. Better therapy is desperately needed for this aggressive disease.     

Eight years experience of local prostate cancer treatment with permanent I seed brachytherapy - Morbidity and outcome results

Background and purpose

There are only a limited number of reports of treatment of prostate cancer with permanent prostate seed I¹²⁵ brachytherapy (PPB) in Europe. We describe results from one Finnish institution having treated 444 patients with a follow-up of eight years.

Material and methods

Morbidity was evaluated by International Prostate Symptom Score and International Index of Erectile Function questionnaires. Urine flow, residual urine volume and the PSA values were measured pre-treatment and during follow-up. Any additional treatments were recorded.

Results

PPB was well tolerated. Median IPSS increased from 8 at baseline to 18 at three months post-therapy and returned to baseline score within 12 months. Median urine flow decreased from 15.2 ml/s at baseline to 10.2 ml/s at three months and returned to baseline value within two years. Acute urinary retention, potency preservation and severe proctitis were observed in 11%, 86% and 2% of patients, respectively. The PSA bounce was observed in 13% and PSA nadir ?0.5 μg/l was reached by 81% of patients. Disease-free survival (DFS) was 90.2%. In the Cox regression analysis, the independent predictors of DFS were risk group and PSA nadir ?0.5 μg/l (p < 0.0001 for both). PC-specific survival was 98.5% and overall survival was 94.6%.

Conclusions

Our results are in concordance and comparable with other reports on PPB.     

Activity of Dutasteride Plus Ketoconazole in Castration-Refractory Prostate Cancer After Progression on Ketoconazole Alone

Background

Ketoconazole is a commonly used secondary hormonal therapy in castration-refractory prostate cancer (CRPC), but disease progression inevitably occurs. Both prostatic and metastatic lesions in patients with CRPC overexpress 5-α reductase (SRDA5) type I. We hypothesized that SRDA5 inhibition in combination with ketoconazole would mitigate progression after treatment with ketoconazole alone.

Patients and Methods

A total of 10 patients with CRPC with progression after ketoconazole treatment were treated with a combination of ketoconazole plus dutasteride 0.5 mg/day, a dual SRDA5 inhibitor.

Results

After dutasteride addition, 8 (80%) of the 10 patients had varying degrees of prostate-specific antigen (PSA) decline relative to baseline. Median progression-free survival after dutasteride addition was 4.9 months (range, 2.7+ to 9.8 months); no patient had a ≤ 50% PSA decline.

Conclusion

We conclude that dutasteride added to ketoconazole at the time progression might prolong time to PSA progression in patients with CRPC.