Clinical Trial: A Phase II Trial of Adjuvant Radiation Therapy With Ifosfamide in Patients With MMT of the Uterus
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Pilot Phase II Trial of Adjuvant Radiation Therapy "Sandwiched" Between Ifosfamide in Patients With Mixed Mesodermal Tumors
Brief Summary:
The optimal sequence and /or modality for adjuvant therapy in the management of MMT clearly remains to be established. The rationale for the protocol is to "sandwich" pelvic radiation with chemotherapy to decrease distant metastasis.
The concept of sequential chemotherapy/radiation therapy/chemotherapy has been previously reported. The chemotherapeutic agents employed in that trial were cisplatin and epirubicin with a reported survival of 74% in patients with Stage I and II MMT with a median follow-up period of 55 months. Toxicity was reported as tolerable and 98% of patients were able to complete their therapy. Sequential chemotherapy/radiation/chemotherapy has also been investigated in other high risk uterine tumors with a propensity for both distant and local recurrence. A retrospective review of 23 patients treated with radiation "sandwiched" between paclitaxel/platinum chemotherapy in patients with uterine papillary serous carcinomas found 5/23 (22%) to have recurred with a median PFI of 16.6 months (range 12.1 - 23 months). The median follow-up was 21 months (range 10-45 months). Of the patients remaining disease-free, the median PFI was 21.4 months (range 10-15 months). Toxicity was acceptable and the regimen was well tolerated. A prospective trial of this regimen is presently ongoing and without unexpected toxicity or morbidity.
The proposed study will sandwich radiation between the two most active chemotherapeutic agents for MMT identified to date (ifosfamide/cisplatin). By doing so, we attempt to decrease both local and distant recurrence, which may translate into an improved progression free interval and possibly even extend survival.
Detailed Summary:
Uterine sarcomas account for only 2-4% of uterine malignancies, yet they are responsible for 26% of uterine cancer deaths. Mixed mesodermal tumors (MMT), previously known as carcinosarcoma, are the most common of the uterine sarcomas in the United States. Prognosis for these patients is generally grim due to the propensity for early metastatic disease. Patterns of spread are by both hematogenous and lymphatic dissemination. It has been noted that 66% of patients with disease clinically confined to the uterus have nodal metastasis at the time of diagnosis. The majority of patients will die with both wide spread intra-abdominal and pelvic disease within two years of diagnosis.
Pelvic failure occurs in up to 50% of patients. Adjuvant pelvic radiation therapy has been advantageous in controlling local recurrence. One study reports 26% local recurrence in patients treated with surgery alone versus 14% recurrence in patients treated with surgery and adjuvant pelvic radiation. Although adjuvant radiation shows a benefit in improving local control, it has not been found to impact survival. This finding is likely attributed to the high incidence of distant metastasis (85%) known to occur with disease recurrence.
Multiple chemotherapeutic agents have been evaluated in the management of advanced, persistent or recurrent uterine MMT. Response to single agent therapy has been less than 35% with the most active agents identified being ifosfamide (response rate = 34.8%) and cisplatin (response rate 17.9%. The use of chemotherapy in the adjuvant setting has been explored as a means of attempting to impact the incidence of distant metastasis. The Gynecologic Oncology Group (GOG) evaluated ifosfamide/cisplatin in the adjuvant setting in patients with completely resected Stage I or II uterine MMT. At a minimum of two years follow-up, 41 pati
Sponsor: Montefiore Medical Center
Current Primary Outcome: To evaluate the toxicity and tolerability of pelvic radiation "sandwiched" between cycles of chemotherapy in patients with MMT. [ Time Frame: 2 years ]
Original Primary Outcome: To evaluate the toxicity and tolerability of pelvic radiation "sandwiched" between cycles of chemotherapy in patients with MMT.
Current Secondary Outcome: To define patterns of recurrence and one-year recurrence-free survival in patients with MMT treated with "sandwich" therapy [ Time Frame: 2 years ]
Original Secondary Outcome: To define patterns of recurrence and one-year recurrence-free survival in patients with MMT treated with "sandwich" therapy
Information By: Montefiore Medical Center
Dates:
Date Received: October 3, 2005
Date Started: February 2003
Date Completion:
Last Updated: April 22, 2012
Last Verified: April 2012
