Intensity Modulated Radiation Therapy With Cisplatin and Gemcitabine to Treat Locally Advanced Cervical Carcinoma

Many studies have investigated multiagent chemotherapy as a means of intensifying treatment.
The results of such trials indicate that gemcitabine has considerable activity against
cervical cancer when given with cisplatin/RT, however, it is quite toxic. The predominant
toxicities are gastrointestinal and hematologic. Methods to reduce gastrointestinal and
hematologic toxicity during chemoradiotherapy could mitigate this toxicity and take advantage
of the therapeutic benefits of gemcitabine

IMRT is an advanced radiation therapy delivery technique that reduces the amount of radiation
given to normal tissues and may therefore reduce unwanted side effects. IMRT tries to lower
the amount of radiation that normal tissues receive, while still delivering the desired
amount of radiation to the cancer cells and other areas, such as lymph nodes. IMRT does this
by using computers to design the best way to aim radiation at the tumor(s), while still
delivering a radiation dose comparable to standard radiation.

Inclusion Criteria:

- Diagnosis: Histologically-proven, invasive primary carcinoma of the cervix.

- Disease Status: Stage IB2-IVA cervical cancer or stage I with biopsy-proven pelvic
node metastases, positive surgical margins, or parametrial extension based upon
standard diagnostic workup, including:

- History/physical examination

- Examination under anesthesia (if indicated)

- Biopsy

- Intravenous pyelogram and/or cystoscopy (if indicated)

- Colonoscopy, sigmoidoscopy, or rigid proctoscopy (if indicated)

- PA and lateral chest x-ray or chest CT

- CT or MRI of the pelvis

- PET, PET/CT, or PET/CT simulation (encouraged)

- Performance Level: Karnofsky Performance Status ≥ 60 - Peripheral ≥ ANC 1500/uL

- Platelet count ≥ 100,000/uL (transfusion independent)

- Hemoglobin ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve
Hgb ≥ 8.0 g/dL is acceptable)

- Serum creatinine ≤ 1.5 mg/dl

- Bilirubin (sum of conjugated + unconjugated) < 1.5 mg/dl, and

- SGPT (ALT) < 1.5 x upper limit of normal (ULN) for age, and

- SGOT (AST) < 1.5 x upper limit of normal (ULN) for age

Exclusion Criteria:

- Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on
this study due to risks of fetal and teratogenic adverse events.(Note: Serum Pregnancy
tests must be obtained in women of child bearing potential). Sexually active females
may not participate unless they have agreed to use an effective contraceptive method
(such as abstinence, diaphragm, condom, or intrauterine device) to prevent pregnancy
for the duration of the study.

- Concomitant Medications, if taken within the last 28 days.

- Growth factor(s): Growth factors that support platelet or white cell number or
function must not have been administered within the past 28 days.

- Erythropoietic drug(s): Erythropoietin or related hormones must not have been
administered within the past 28 days.

- Infection: Patients who have an uncontrolled infection.

- Evidence of para-aortic lymphadenopathy or distant metastases

- Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free
for a minimum of 3 years.

- Prior systemic chemotherapy within the last three years.

- Prior radiotherapy to the pelvis

- Allergic to iodinated contrast if undergoing a contrast enhanced CT scan of the pelvis