Atif M. Hussein

Chemotherapy with cisplatin and 5-fluorouracil for penile and urethral squamous cell carcinomas

Six men with either recurrent (n = 4) or unresectable (n = 2) squamous cell carcinoma of the penis (n = 5) and urethra (n = 1) received chemotherapy with cisplatin intravenously at a dose of 100 mg/m2. This was followed 24 hours later by a continuous intravenous infusion of 5‐fluorouracil (5‐FU) at a dose of 960 mg/m2/d for five days every 3 to 4 weeks. There was universal alopecia. The other toxicities were mild and consisted of mucositis, nausea, vomiting, reversible creatininemia, and transient azotemia. After chemotherapy, five patients had a clinical partial response and one had a complete response. Of the five patients with no metastases, three had residual unresectable tumors. These three patients received radiation and survived for 6,8, and 20 months after the start of chemotherapy. The other two patients were rendered disease‐free by surgery. The first patient, who was a partial responder to chemotherapy, survived for 26 months. The second patient, who was a clinical complete responder, had excision of microscopic disease and is disease‐free at 32+ months after the start of chemotherapy. This is the first article to report that the combination of cisplatin and 5‐FU is active in penile and urethral carcinomas. After chemotherapy, surgery may be useful in selected patients to accurately assess response and excise localized residual tumors. Patients rendered tumor‐free may achieve long‐term survival.

Tumor Lysis Syndrome After Induction Chemotherapy in Small-cell Lung Carcinoma

Small-cell lung cancer (SCLC) is responsive to combination chemotherapy. Response rates of 50–80% can be achieved depending on whether the cancer is limited or extensive. Rarely, patients with SCLC respond so rapidly to induction chemotherapy that they develop a tumor lysis syndrome. This syndrome may lead to azotemia and renal failure if not recognized early and treated appropriately. This complication of therapy is important to recognize as the treatment of SCLC is sometimes administered on an outpatient basis. In addition, certain chemotherapeutic agents used in SCLC, such as cis- platin, are nephrotoxic and could potentially aggravate the azotemia secondary to the tumor lysis syndrome.

Combination chemotherapy and radiotherapy for small-cell carcinoma of the esophagus: A case report of long-term survival and review of the literature

Small-cell carcinoma of the esophagus is a rare tumor and has received little attention until recent years. It should be differentiated from the far more common poorly differentiated squamous-cell carcinoma of the esophagus, because treatment by surgical resection alone or by radiation therapy results in limited survival of a few months. It is now recognized that esophageal small-cell carcinoma presents with early widespread dissemination and is chemosensitive, similar to primary small-cell carcinoma of the lung. We report on a patient with small-cell carcinoma of the esophagus treated with combination chemotherapy consisting of cyclophosphamide, vincristine, and VP-16 followed by local radiation therapy. Pathologic complete remission was achieved. The patient is currently in remission 22 months after diagnosis, the longest survival reported thus far.

Activity of pirarubicin (4′‐o‐tetrahydropyranyladriamycin) in malignant mesothelioma

Eight patients with diffuse malignant mesothelioma of the pleura or peritoneum, previously untreated with chemotherapy, were treated with a new anthracycline 4′‐O‐tetrahydropyranyladriamycin (pirarubicin). Pirarubicin was given intravenously at the rate of 5 mg per minute, at doses ranging from 35 to 70 mg/m2 once every 21 days. On clinical evaluation, one patient had complete response lasting 4 months. On second‐look laparotomy residual tumor was found and she was labelled a partial responder and changed to alternate chemotherapy. Another patient had a partial response of recurrent chest wall tumors lasting 11 months. A third patient had a partial response lasting 4+ months of a pleural‐based tumor and resolution of pleural effusion. After the fifth course of chemotherapy, he developed severe granulocytopenia, pseudomonas sepsis, shock, and renal failure. Despite recovery of blood counts to normal within 3 days, renal failure proved fatal. Autopsy revealed only fibrosis and no gross or microscopic evidence of malignant mesothelioma. A fourth patient had improvement in evaluable disease lasting about 4 months; and the remaining four had stable disease for at least 2 months each. The authors conclude that, whenever feasible, noninvasive clinical assessment of tumor response should be supplemented by surgical‐pathologic evaluation. Pirarubicin is active in malignant mesothelioma. This is the first report documenting complete tumor eradication after chemotherapy in an adult with malignant mesothelioma.

Brain metastases in malignant pleural mesothelioma. Case report and review of the literature.

Recent advances in pleural malignant mesothelioma include the sequential use of palliative surgery, perioperative radiation therapy, and systemic chemotherapy. Radical treatments may not only palliate but also improve survival in some patients. The latter may be associated with the appearance of metastases in unusual sites including the central nervous system. In malignant mesothelioma, brain metastases were previously reported in 19 patients at autopsy and in only 1 patient antemortem. We detail the clinical presentation in the second patient with pleural malignant mesothelioma thus far reported to develop brain metastases. The difficulties in diagnosis, the role of immunoperoxidase stains in malignant mesothelioma, excellent tolerance of different modalities of treatment, and a review of the literature of brain metastases in mesothelioma are discussed. Based on our report, the possibility of brain metastases should be investigated by careful clinical examination prior to a radical treatment in patients with progressive refractory mesothelioma.

Small cell carcinoma of the large intestine presenting as central nervous systems signs and symptoms. Two case reports with literature review.

Extrapulmonary small cell carcinoma is rare. Small cell carcinoma of the colorectum has been reported in 73 patients. Patients with colorectal small cell carcinoma present with signs and symptoms related to the primary site. Usually patients present with advanced stage. Rarely do patients with colorectal small cell carcinoma present with signs and symptoms related to the central nervous system (CNS). We report two patients who presented with CNS signs. The two patients underwent craniotomy for definitive diagnosis and resection in one patient. In both cases, pathology was consistent with pure small cell carcinoma. Postoperatively, a search for a primary revealed the rectum and the hepatic flexure of the colon to be the sites. Patients were started on combination chemotherapy. One patient achieved a complete remission and the second is currently receiving chemotherapy with a partial response. This is the first report of colorectal small cell carcinoma presenting as CNS lesion(s).

Carcinomatous meningitis from transitional cell carcinoma of the bladder (case report)

SummaryIn the past decade, there has been an increasing awareness of central nervous system metastases as a frequent complication of some malignancies, particularly in lung, breast and hematologic cancers. However, the central nervous system remains an uncommon location for metastases from certain primary tumors including those from the genitourinary system. We report on a patient with transitional cell carcinoma of the bladder who was treated with combination chemotherapy, and during the course of his disease developed carcinomatous meningitis. We anticipate this unusual complication of bladder transitional cell carcinoma will be seen more frequently, especially in the light of available data from effective chemotherapeutic regimens. We report this patient to alert physicians to this complication and to consider using prophylactic measures in responding patients as is the case in other malignancies.

Phase II trial of 4'-O-tetrahydropyranyladriamycin (Pirarubicin) in head and neck carcinoma

Background. 4′‐O‐tetrahydropyranyladriamycin (Pirarubicin, Meiji Seika (USA) Inc., New York, NY) may be less toxic than doxorubicin.

Carcinoid tumor presenting as central nervous system symptoms. Case report and review of the literature.

Carcinoid tumors arc relatively uncommon. They are known for their slow growing behavior and unique symptoms. Patients with carcinoid tumors usually present with signs and symptoms due either to local disease or to the carcinoid syndrome. During the course of these tumors, they tend to metastasize to different sites, including regional lymph nodes, lungs, liver, and bone. They rarely metastasize to the central nervous system (CNS) and very rarely present with signs and symptoms related to CNS metastasis. We report a patient who presented with CNS symptoms and was found to have a pulmonary carcinoid tumor involving the liver and the dura mater. In this article, CNS involvement in carcinoid tumors is discussed, and the literature is reviewed.

Five-Drug Antiemetic Combination for Cisplatin Chemotherapy

A combination of metoclopramide, dexamethasone, droperidol, lorazepam, and diphenhydramine was used in prophylaxis of high-dose (greater than or equal to 100 mg/m2) or moderate dose (greater than or equal to 50 mg/m2) cisplatin. Sixty minutes prior to starting cisplatin, 16 mg dexamethasone, 50 mg diphenhydramine, and 0.5 mg lorazepam were given orally (PO). Droperidol 1 mg was given intramuscularly (IM) 15 minutes prior to beginning cisplatin. Repetitive doses of intravenous (IV) metoclopramide, 2 mg/kg in 75 ml 5% dextrose in water over 15 minutes was given 30 minutes prior to, and at 1 1/2, 4 1/2, and 7 1/2 hours after beginning cisplatin chemotherapy. Only patients with nausea and/or vomiting received subsequent doses of 2 mg/kg metoclopramide IV every 3 hours as needed. Patients refractory to metoclopramide were given 1 mg droperidol IM and 50 mg of diphenhydramine PO every 6 hours. There were 19 men and 9 women with a median age of 58 (range 31-75) years. Complete protection from nausea and vomiting in all courses of treatment occurred in 17 (61%) patients. In 63% and 70% of the 57 evaluable courses, there was neither nausea nor vomiting, during the first 24 hours after cisplatin. When present, nausea was mild and the median number of vomiting episodes was 2 (range 1-3). This antiemetic regimen was well tolerated. Toxicities were mild and occurred in 3 patients (angioneurotic edema, transient episode of facial twitching, and heaviness of tongue, respectively). The 5-drug antiemetic combination can prevent cisplatin-induced nausea and vomiting in a majority of patients.