Neoadjuvant Chemotherapy for Patients With Squamous Cell Carcinoma of the Penis
Neoadjuvant Chemotherapy for Patients With Squamous Cell Carcinoma of the Penis
Primary Objective:

 -To evaluate the feasibility and efficacy of multimodality treatment (neoadjuvant
 chemotherapy prior to extirpative surgery) for clinical stage TXN2-3M0 squamous cell
 carcinoma of the penis.
Before treatment starts, participants will have a complete exam, including blood and urine
 tests. A CT scan of the abdomen and pelvis will be done. Participants will have a chest
 x-ray, bone scan, and an EKG (heart test). A special heart function test may also need to be
 done in some participants. If necessary a biopsy of enlarged lymph node(s) will be obtained
 prior to treatment.

 Blood tests will be repeated once a week during treatment. CT scans of the abdomen and pelvis
 and a Chest x-ray will be done after 2 treatments with Taxol, Ifosfamide, and Cisplatin.
 These will also be done before surgery.

 The drugs Taxol, Ifosfamide and Cisplatin will be given through a catheter (plastic tube)
 placed in a vein in the arm or under the collarbone. Taxol will be given over 3 hours the
 first day of the treatment cycle. To prevent an allergic reaction, before the Taxol is given,
 the participant will receive three drugs. These are Dexamethasone, Diphenhydramine, and
 either Cimetidine or Ranitidine.

 After Taxol, Ifosfamide will be given over 2 hours every day for the first three days of the
 treatment cycle. To prevent possible irritation of Ifosfamide to the bladder, participants
 will also receive Mesna through the plastic catheter. Mesna will be given both before and
 after Ifosfamide every day. Mesna is not chemotherapy. It is a medication to prevent side
 effects of Ifosfamide into the bladder.

 Every day for the first three days of the cycle, and after Ifosfamide is given, participants
 will also receive Cisplatin through the catheter at a steady rate over 2 hours, along with
 Mannitol and salt water to flush the kidneys. This treatment will be given in the hospital
 and will require staying in the hospital for 3-4 days. It will be repeated for a total of 4
 times; once every 21 days, if the participant has high enough numbers of white blood cells
 and platelets.

 Participants may be given injections of G-CSF under the skin once a day for up to 7 days
 (days 6-12 of the cycle) to bring the white cells up faster after the chemotherapy. This will
 also lower the risk of severe infections.

 After completing 4 treatments of chemotherapy, participants will have blood and urine tests,
 a chest x-ray to learn the response of the tumor to the chemotherapy. They will also have a
 CT scan of the abdomen and pelvis. Participants who have a response to the chemotherapy, or
 show no sign of new spread of the cancer to other parts of the body, will then have surgery.
 Surgery will be done to remove the tumor. The lymph nodes in the groin will be removed. The
 pelvic lymph nodes may also need to be removed. How much tissue is removed depends on how far
 the tumor has spread. The surgeons will explain the specifics of the surgery in a separate
 consent form.

 After completion of the treatment, physical exams, CT scans, chest x-rays, blood tests, and
 urine tests will be done every 3 months for 2 years. They will then be done every 6 months.
 These procedures can be done by a physician at M. D. Anderson or by the participant's own
 doctor. If the participant's doctor does it, the information will need to be forwarded to the
 doctors at M. D. Anderson. Participants will be expected to come to M. D. Anderson or to
 their respective participating urologist/medical oncologist at least once every 6 months for
 a check-up.

 This is an investigational study. The FDA has approved Taxol, Ifosfamide, Cisplatin, and
 Mesna. Up to 40 participants will take part in this study. All will be enrolled at M. D.
 Anderson.
Inclusion Criteria:

 1. Written informed consent must be obtained from each patient prior to study entry.

 2. Age >/= 14 years of age. Life expectancy greater than or equal to 6 months. PS </= 2
 (ECOG).

 3. Patients with histologically confirmed squamous cell carcinoma of the penis who
 present with clinical stage (T(subscript)xN(subscript)2-3M(subscript)0) disease based
 on the 1987-1992 TNM Staging System and meeting the additional clinicopathologic
 criteria as defined in the protocol (section 3.1).

 4. Patients must have adequate physiologic reserve as evidenced by: absolute neutrophil
 count (ANC) >/= 1,500/mm3(superscript) and platelet count >/= 100,000/mm3.
 Transaminases </= 2 times the upper limit of normal. Conjugated bilirubin </=
 1.5mg/dL. Creatinine clearance (either calculated or measured) of >/= 40ml/minute.

 5. No evidence of active ischemia on the EKG and, for patients with significant prior
 coronary artery disease history, an ejection fraction of more than 40%. No evidence of
 severe conduction abnormalities on EKG.

 Exclusion Criteria:

 1. Patients with uncontrolled infection or CNS disease.

 2. Distant metastasis (TNM stage M1, i.e., lung, bone, other visceral sites, lymph node
 metastasis above the aortic bifurcation).

 3. Patients with clinically negative inguinal examinations or those with palpable
 adenopathy not meeting pathological or clinical criteria (i.e., minimal nodal
 metastasis or false positive inguinal examination).

 4. Prior systemic chemotherapy for penile carcinoma.

 5. Prior radiation therapy to inguinal or pelvic lymph nodes.