Tuesday, September 22, 2009

Escalated-Dose BEACOPP in the Treatment of Patients With Advanced-Stage Hodgkin's Lymphoma: 10 Years of Follow-Up of the GHSG HD9 Study [Hematologic Malignancies]

10 year HD9 results are published in this weeks JCO. To review this is a trial from the German Hodgkin Study group looking at differing chemotherapy regimens in unfavorable advanced HL. Escalated BEACOPP continues to out perform the other arms for DFS and OS, at the cost of dramatic increases in hematopoetic toxicity. One thing to keep in mind with this trial is that RT was used in 70% of these patients. Another item worth considering is the secondary malignancy rate ~6%, and this in crude numbers!

Link and Abstract
Escalated-Dose BEACOPP in the Treatment of Patients With Advanced-Stage Hodgkin's Lymphoma: 10 Years of Follow-Up of the GHSG HD9 Study [Hematologic Malignancies]: "Purpose

The HD9 trial of the German Hodgkin Study Group compared two different doses (baseline and escalated) of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) chemotherapy regimen in 1,196 patients with advanced-stage Hodgkin's lymphoma (HL). The previous analysis with 5 years median follow-up had indicated improved tumor control with BEACOPP escalated. Since the long-term safety and efficacy of this regimen has been debated, we report the 10-year follow-up.

Patients and Methods

Patients received one of three chemotherapy regimens: eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); eight cycles of BEACOPP baseline; or eight cycles of BEACOPP escalated.

Results

Median follow-up was 111 months. At 10 years, freedom from treatment failure (FFTF) was 64%, 70%, and 82% with OS rates of 75%, 80%, and 86% for patients treated with COPP/ABVD (arm A), BEACOPP baseline (arm B), and BEACOPP escalated (arm C), respectively (P < .001). BEACOPP escalated was significantly better than BEACOPP baseline in terms of FFTF (P < .0001) and OS (P = .0053). A total of 74 second malignancies (6.2%) were documented, including acute myeloid leukemia (0.4%, 1.5%, and 3.0%), non-Hodgkin's lymphoma (2.7%, 1.7%, and 1.0%), and solid tumors (2.7%, 3.4%, and 1.9%). The corresponding overall secondary malignancy rates were 5.7%, 6.6%, and 6.0%, respectively.

Conclusion

The 10-year follow-up of the HD9 trial demonstrates a stabilized significant improvement in long-term FFTF and OS for BEACOPP escalated in advanced-stage HL. These results challenge ABVD as standard of care for this patient population.

"

Tuesday, September 1, 2009

Talampanel With Standard Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma: A Multicenter Phase II Trial [Neurooncology]

Big week for RT in this weeks JCO: Interesting article looking at a novel therapeutic in GBM. Talampanel is a inhibitor of a glutamatergic excitatory pathway that GBMs seem to use for proliferation and survival. Their results with the addition of talampanel to TMZ + RT are favorable when compared to the EORTC (Stupp) trial which established the current standard of care, especially considering that the percent of methylated MGMT was lower in the current study. Phase III confirmation is planned.

Talampanel With Standard Radiation and Temozolomide in Patients With Newly Diagnosed Glioblastoma: A Multicenter Phase II Trial [Neurooncology]:
"Purpose

Recent data suggest that the glutamatergic system is important in the proliferation and migration of glioblastoma. Talampanel is a well-tolerated, oral -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker that could be beneficial in this disease.

Patients and Methods

This trial was designed to estimate overall survival in adults with newly diagnosed glioblastoma treated with talampanel in addition to standard radiation (RT) and temozolomide (TMZ). A secondary purpose was to evaluate talampanel toxicity in this setting. Talampanel was initiated with RT + TMZ and discontinued for toxicity or disease progression. Survival was compared with historical controls.

Results

Seventy-two patients were enrolled from December 2005 to July 2006. Their median age was 60 years (range, 37 to 85 years, with 17% > 70 years), median Karnofsky performance score was 90 (range, 70 to 100), and 77% had a debulking procedure. With a median follow-up time of 18 months, 55 patients (76%) have died, yielding a median survival time of 18.3 months (95% CI, 14.6 to 22.5 months). When the 60 patients who were 18 to 70 years old were compared with the European Organisation for Research and Treatment of Cancer (EORTC) RT + TMZ data, the median survival (20.3 v 14.6 months, respectively) and percentage of patients surviving at 24 months (41.7% v 26.5%, respectively; P = .02) seemed superior. The percentage of patients methylated at O6-methylguanine–DNA methyltransferase was lower than on the EORTC study (29% v 43%, respectively). Talampanel was well tolerated and did not increase the known hematologic or nonhematologic toxicities of TMZ.

Conclusion

Talampanel can be added to RT + TMZ without significant additional toxicity. The encouraging survival results in methylated and unmethylated patients suggest that blocking AMPA receptors may be a useful strategy in newly diagnosed glioblastoma.

"

Phase II Study of Bevacizumab With Concurrent Capecitabine and Radiation Followed by Maintenance Gemcitabine and Bevacizumab for Locally Advanced Pancreatic Cancer: Radiation Therapy Oncology Group RTOG 0411 [Gastrointestinal Cancer]

This weeks JCO: RTOG 0411 reports out for bevacizumab + capcitabine + RT for unresectable pancreatic cancer followed by gem + bev, resulting in disappointing survival numbers. Pancreas remains a site where the field is open and in desperate need of novel therapies and approaches.


Link and Abstract:

Phase II Study of Bevacizumab With Concurrent Capecitabine and Radiation Followed by Maintenance Gemcitabine and Bevacizumab for Locally Advanced Pancreatic Cancer: Radiation Therapy Oncology Group RTOG 0411 [Gastrointestinal Cancer]:
"Purpose

The primary objective of this study was to assess the 1-year survival of patients with locally advanced, unresectable pancreatic cancer treated with the combination of bevacizumab, capecitabine, and radiation. Secondary end points were toxicity, progression-free survival (PFS), and response rate (RR).


Patients and Methods

Patients with locally advanced pancreatic cancer without duodenal invasion were treated with 50.4 Gy per 28 fractions to the gross tumor with concurrent capecitabine 825 mg/m2 orally twice daily on days of radiation and bevacizumab 5 mg/kg on days 1, 15, and 29 followed by maintenance gemcitabine 1 g/m2 weekly for 3 weeks and bevacizumab 5 mg/kg every 2 weeks, both in 4-week cycles until progression. Treatment plans were reviewed for quality assurance (QA).


Results

Between January 2005 and February 2006, 82 eligible patients were treated. The median and 1-year survival rates were 11.9 months (95% CI, 9.9 to 14.0 months) and 47% (95% CI, 36% to 57%). Median PFS was 8.6 months (95% CI, 6.9 to 10.5), and RR was 26%. Overall, 35.4% of patients had grade 3 or greater treatment-related gastrointestinal toxicity (22.0% during chemoradiotherapy, 13.4% during maintenance chemotherapy). Unacceptable radiotherapy protocol deviations (ie, inappropriately generous volume contoured) correlated with grade 3 or greater gastrointestinal toxicity during chemoradiotherapy (45% v 18%; adjusted odds ratio, 3.7; 95% CI, 0.98 to 14.1; P = .05).


Conclusion

The addition of bevacizumab to chemoradiotherapy followed by bevacizumab and gemcitabine resulted in a similar median survival to previous Radiation Therapy Oncology Group studies in patients with locally advanced pancreatic cancer. Prospective QA may help limit toxicity in future trials.

"

Trends in Mastectomy Rates at the Mayo Clinic Rochester: Effect of Surgical Year and Preoperative Magnetic Resonance Imaging [Breast Cancer]

This weeks JCO has a provocative article about the use of MRI in the preoperative evaluation of breast cancer. Without any clinical evidence of improved outcomes (survival, local control, etc), breast MRI has been much more utilized in the last 5 years. One effect that this manuscript clearly demonstrates is that more people are receiving mastectomies...

Link and Abstract below:

Trends in Mastectomy Rates at the Mayo Clinic Rochester: Effect of Surgical Year and Preoperative Magnetic Resonance Imaging [Breast Cancer]:
"Purpose

Recent changes have occurred in the presurgical planning for breast cancer, including the introduction of preoperative breast magnetic resonance imaging (MRI). We sought to analyze the trends in mastectomy rates and the relationship to preoperative MRI and surgical year at Mayo Clinic, Rochester, MN.


Patients and Methods

We identified 5,405 patients who underwent surgery between 1997 and 2006. Patients undergoing MRI were identified from a prospective database. Trends in mastectomy rate and the association of MRI with surgery type were analyzed. Multiple logistic regression was used to assess the effect of surgery year and MRI on surgery type, while adjusting for potential confounding variables.


Results

Mastectomy rates differed significantly across time (P < .0001), and decreased from 45% in 1997% to 31% in 2003, followed by increasing rates for 2004 to 2006. The use of MRI increased from 10% in 2003% to 23% in 2006 (P < .0001). Patients with MRI were more likely to undergo mastectomy than those without MRI (54% v 36%; P < .0001). However, mastectomy rates increased from 2004 to 2006 predominantly among patients without MRI (29% in 2003% to 41% in 2006; P < .0001). In a multivariable model, both MRI (odds ratio [OR], 1.7; P < .0001) and surgical year (compared to 2003 OR: 1.4 for 2004, 1.8 for 2005, and 1.7 for 2006; P < .0001) were independent predictors of mastectomy.

Conclusion

After a steady decline, mastectomy rates have increased in recent years with both surgery year and MRI as significant predictors for type of surgery. Further studies are needed to evaluate the role of MRI and other factors influencing surgical planning."

Late Pelvic Toxicity After Bladder-Sparing Therapy in Patients With Invasive Bladder Cancer: RTOG 89-03, 95-06, 97-06, 99-06 [Genitourinary Cancer]

In this weeks JCO there is a great article on the QOL results with the sequential RTOG Bladder preservation trials. Link and abstract below:

Late Pelvic Toxicity After Bladder-Sparing Therapy in Patients With Invasive Bladder Cancer: RTOG 89-03, 95-06, 97-06, 99-06 [Genitourinary Cancer]:
"Purpose

In selected patients with muscle-invasive bladder cancer, combined-modality therapy (transurethral resection bladder tumor [TURBT], radiation therapy, chemotherapy) with salvage cystectomy, if necessary, can achieve survival rates similar to radical cystectomy. We investigated late pelvic toxicity after chemoradiotherapy for patients treated on prospective protocols.

Patients and Methods

Between 1990 and 2002, 285 eligible patients enrolled on four prospective protocols (Radiation Therapy Oncology Group [RTOG] 8903, 9506, 9706, 9906) and 157 underwent combined-modality therapy, surviving ≥ 2 years from start of treatment with their bladder intact. Rates of late genitourinary (GU) and GI toxicity were assessed using the RTOG Late Radiation Morbidity Schema, with worst toxicity grade (scale 0 to 5) occurring ≥ 180 days after start of consolidation therapy reported for each patient. Persistence of toxicity was defined as grade 3+ toxicity not decreasing by at least one grade. Logistic and Cox regression analyses were performed to evaluate relationship between clinical characteristics, frequency, and time to late grade 3+ pelvic toxicity. Covariates included age, sex, stage, presence of carcinoma in situ, completeness of TURBT, and protocol.

Results

Median follow-up was 5.4 years (range, 2.0 to 13.2 years). Seven percent of patients experienced late grade 3+ pelvic toxicity: 5.7% GU and 1.9% GI. In only one of nine patients did a grade 3+ GU toxicity persist. Notably there were no late grade 4 toxicities and no treatment-related deaths. None of the clinical variables studied predicted for late grade 3+ pelvic toxicity.

Conclusion

Rates of significant late pelvic toxicity for patients completing combined-modality therapy for invasive bladder cancer and retaining their native bladder are low."