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A Pilot Phase II Trial of Radiation Therapy "Sandwiched" Between Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma

Phase 2
18 Years
Not Enrolling
Uterine Cancer

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Trial Information

A Pilot Phase II Trial of Radiation Therapy "Sandwiched" Between Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma

Uterine papillary serous carcinoma (UPSC) is an uncommon, but aggressive variant of
endometrial carcinoma that has a high recurrence rate and poor response to therapy. It has
a propensity to metastasize throughout the abdomen, similar to serous carcinoma of the
ovary. In fact, many patients with disease apparently confined to the uterus have
microscopic intra-abdominal spread at the time of diagnosis. Recurrences are common both in
the pelvis as well as in the upper abdomen.

After staging and debulking of gross disease, adjuvant radiation therapy is recommended to
treat patients with endometrial carcinoma at high risk for recurrent disease. High-risk
features include histologic cell type, grade, depth of myometrial invasion, cervical
extension, lymph-vascular invasion, adnexal involvement, intraperitoneal spread, positive
peritoneal cytology, and positive lymph nodes. Pelvic radiation can limit local recurrences
to less than 6.5%. However, approximately 25-30% of patients with high-risk features who
receive radiation recur with distant metastases. Even patients treated with whole abdominal
irradiation are at risk for extra-abdominal recurrences with progression-free intervals of 7
to 8 months.

Adjuvant chemotherapeutic regimens have been studied in high-risk endometrial cancers, but
none have demonstrated a survival advantage. Doxorubicin, in combination with platinum, has
a reported 42% response rate, but a high toxicity profile. Paclitaxel has an overall
response rate of 36% in patients with advanced and recurrent endometrial cancer.
Platinum-based chemotherapies have a 28-42% response rate.

Retrospective studies in patients with UPSC have demonstrated response rates of up to 35% in
patients with multiagent chemotherapy. In one study, a median progression-free interval of
30 months was observed in patients treated with paclitaxel and platinum in the adjuvant and
recurrent settings. Based on these findings and the similarities and clinical success of
paclitaxel/platinum therapy in patients with ovarian serous carcinoma, this combination
warrants further investigation in a prospective manner in patients with UPSC.

Combination chemo/radiotherapy trials in advanced/recurrent endometrial cancer are ongoing.
The optimal radiation modality, chemotherapeutic agents, and sequence of these regimens for
the treatment of UPSC are yet to be established. A retrospective review of 16 patients
treated at our institution with the sequential use of radiation "sandwiched" between
paclitaxel/platinum chemotherapy found only one patient to have recurred at 16 months with a
median follow-up of 15 months (range 6-33 months). The regimen was well tolerated. Eight of
the sixteen patients (50%) developed grade 3 neutropenia following cycle 4 of chemotherapy,
two of which required a 1 week treatment delay. There were no cases of grade 3 or 4
thrombocytopenia noted. There was no febrile neutropenia and no hospital admissions for
toxicity. There were no observed grade 3 or 4 non-hematologic toxicities. With the median
follow up of 15 months, we have not observed late toxicities.

Given these favorable preliminary findings, supported by recently published data documenting
efficacy of the "sandwich" multimodality technique in other difficult uterine malignancies
(malignant mixed mullerian tumors), we propose to study this combination of chemotherapy and
radiation prospectively. Our aim is to better evaluate patterns of recurrence and possible
benefits in progression-free and overall survival.

Surrogate endpoint biomarkers such as ER/PR, HER2/Neu and p53 will be correlated with
prognosis. In addition, fresh frozen tissue will be banked for future cDNA microarray
analyses of UPSC tumors.

Inclusion Criteria:

1. Histologically documented uterine papillary serous carcinoma (UPSC) with no visible
residual disease.

2. Surgical staging to include total abdominal hysterectomy, bilateral
salpingo-oophorectomy, peritoneal washings, and lymph node samplings.

3. Age > 18 years.

4. ECOG performance status of < 2.

5. Written voluntary informed consent.

Exclusion Criteria:

1. Patient has impairment of hepatic, renal or hematologic function as defined by the
following baseline laboratory values:

1. Serum SGOT and /or SGPT > 2.5 times the institutional upper limit of normal

2. Total serum bilirubin > 1.5 mg/dl

3. History of chronic or active hepatitis

4. Serum creatinine > 2.0 mg/dl

5. Platelets < 100,000/mm3

6. Absolute neutrophil count (ANC) < 1500/mm3

7. Hemoglobin < 8.0 g/dl (the patient may be transfused prior to study entry)

2. Patient has severe or uncontrolled concurrent medical disease (eg. uncontrolled
diabetes, unstable angina, myocardial infarction within 6 months, congestive heart
failure, etc.)

3. Patient has been treated with myelosuppressive chemotherapy within three weeks prior
to study entry.

4. Patient with any prior chemotherapy or radiotherapy for pelvic malignancy.

5. Patients with dementia or altered mental status that would prohibit the giving and
understanding of informed consent at the time of study entry.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate the toxicity and tolerability of pelvic radiation "sandwiched" between cycles of paclitaxel/carboplatin chemotherapy in patients with UPSC

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Mark H Einstein, M.D., M.S.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Montefiore Medical Center and Albert Einstein College of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

December 2001

Completion Date:

July 2011

Related Keywords:

  • Uterine Cancer
  • Uterine Papillary Serous Carcinoma
  • UPSC
  • Radiation Therapy
  • Chemotherapy
  • Carcinoma
  • Uterine Neoplasms
  • Cystadenocarcinoma, Serous



Montefiore Medical Center Bronx, New York  10467-2490