Bernard R. Greenberg

Empiric chemotherapy in patients with carcinoma of unknown primary site.

Analysis of the results of chemotherapy in patients with carcinoma of unknown primary site is complicated by the small sizes of most treatment series and patient heterogeneity. Careful evaluation of clinical and pathologic information may identify patients with a relatively high likelihood of response to systemic therapy. This includes patients in whom immunohistochemical studies or electron microscopy, or both, suggest a likely tumor type responsive to systemic therapy, such as prostate cancer, lymphoma, or a neuroendocrine tumor. Clinical evaluation can also identify potentially responsive patients, particularly those with clinical features in common with the extragonadal germ cell tumor syndrome. For patients who do not fit into these more treatable categories, most combination chemotherapy programs have response rates of less than 30% and median survivals of less than one year. Randomized trials have not established any clearly superior chemotherapy program. Regimens containing both Adriamycin (doxorubicin) and mitomycin-C produce response rates of approximately 25% but are associated with the possibility of severe hematologic toxicity, and rarely a syndrome resembling the hemolytic-uremic syndrome. The choice between chemotherapy and supportive care only must be individualized, and the latter option is appropriate for many patients. More detailed clinical and pathologic analyses in conjunction with clinical trials, particularly employing newer diagnostic techniques, are vital to provide better prospective data from which to identify relevant clinical subsets that allow an estimate of an individual patients likelihood of response and the suitability of systemic chemotherapy.

Treatment of Advanced Pancreatic Adenocarcinoma with 5-FU, Leucovorin, Interferon-α-2b, and Cisplatin

Previous laboratory and clinical studies support the ability of interferon (IFN) to enhance the antitumor properties of chemotherapy agents, including cisplatin and 5-fluorouracil (5-FU). A phase I-II clinical trial was initiated to treat several tumor types with IFN-alpha-2b, cisplatin, 5-FU, and leucovorin (LV), given daily for 5 days of a 28-day cycle. Because of preliminary results, this was continued as a phase II trial in 18 patients with metastatic adenocarcinoma of the pancreas. Each treatment day consisted of IFN 5 million u/m2 s.c. (maximum, 10 million U), CDDP 20 mg/m2 i.v. over 1 h, LV 20 mg/m2 i.v.p., and 5-FU 250-275 mg/m2 i.v.p. All patients had measurable disease with no prior chemotherapy for metastatic disease, and all had an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Six of the 16 patients evaluable for response had partial responses (PRs) (37.5%) with a median response duration of 4 months, and all responding patients survived > or = 8 months. Median survival of all 18 treated patients was 5 months. Severe gastrointestinal toxicity (nausea, diarrhea, or requirement for i.v. hydration) was common. Grade 4 hematologic toxicity was seen in six patients. The response rate observed is promising and supports the concept that IFN may potentiate the effects of standard chemotherapy agents. However, the toxicities observed with this dosage schedule were considerable and further studies are needed to develop a less toxic regimen.

Aortic wall sarcoma with tumor emboli and peripheral ischemia : Case report with review of literature

Primary malignant tumors of the aorta are rare, only a handful of isolated cases having been described in the literature. Preoperative diagnosis of these tumors is more the exception than the rule. Diagnosis of aortic tumors is difficult as they can mimic many diverse conditions including atherosclerosis. We report a patient who presented with lower extremity claudication, renal infarction, and diffuse atherosclerosis and who was found to have tumor fragments in blood clots but no evidence of a primary tumor. Immunohistochemistry narrowed the differential diagnosis to a type of sarcoma. Six months later, he developed right flank pain due to a malignant fibrous histiocytoma that involved the abdominal aorta and that had initially manifested as tumor emboli.

Metastatic cancer with unknown primary

Close cooperation between an experienced pathologist and oncologist is essential in the management of patients with unknown primary carcinoma. A comprehensive pathological examination is crucial and, with undifferentiated tumors, this will include immunohistology and/or electron microscopy. Ample properly processed tissue therefore must be provided. Time-consuming and costly radiographic and imaging studies should be avoided. No matter how extensive the evaluation, in a majority of cases, the primary site will never be found, so a selective search for treatable tumors is most appropriate and cost-effective. With adenocarcinomas, this will include prostate, breast, and ovary; for undifferentiated tumors, small cell bronchogenic carcinoma, lymphomas, and germ cell tumors. Table 4 summarizes recommended studies for diagnosing unknown primary undifferentiated or adenocarcinomas. Women with adenocarcinoma in axillary nodes without a primary site should be treated as having breast cancer. Estrogen and progesterone receptor assays are to be obtained on the axillary biopsy. High and midcervical nodes with metastatic squamous cell carcinoma can be treated effectively and, not infrequently, cured with surgery and radiation therapy, even if the primary site never is detected. If doubt remains, treatment should be selected that offers the best chance of significant palliation or cure--for example, cisplatin-based chemotherapy in possible extragonadal germ cell tumors.

Phase II trial of trimetrexate for patients with advanced gastric carcinoma: an Eastern Cooperative Oncology Group study (E1287).

BACKGROUNDnA Phase II study was conducted to evaluate the response, duration of response, and duration of survival of patients with measurable gastric carcinoma treated with trimetrexate (TMTX) who had not had prior chemotherapy.nnnMETHODSnThirty-three patients with unresectable or metastatic gastric adenocarcinoma who had not received previous chemotherapy were treated with intravenous TMTX 12 mg/m(2) daily for 5 days. The dosage of TMTX was reduced to 8 mg/m(2) daily for 5 days for those who had received prior radiotherapy. The cycle was repeated every 3 weeks until disease progression or unacceptable toxicity occurred.nnnRESULTSnThirty-three patients could be analyzed with follow-up data. There was one Grade 5 (lethal) toxicity and four Grade 4 toxicities. Hematologic toxicity was the most common. The overall response rate was 21%, the overall median progression free survival was 2.7 months, and the overall median survival was 5.9 months for the entire cohort. No patients were alive at last follow-up.nnnCONCLUSIONSnThough TMTX as a single agent has activity in gastric carcinoma with manageable toxicity, it cannot be recommended for routine use as a single agent due to the brief duration of response and median survival.

Variability of the thymidine labeling index in squamous cell carcinoma of the head and neck

Tritiated thymidine (3HTdR) labeling is the standard technique for determining the kinetic activity of tumors. This method has been used to label multiple sections of tumor specimens obtained from seven patients with advanced squamous cell carcinoma of the head and neck. Considerable variability was observed in the labeling index in different sites from the same specimen. To reduce the large sampling error due to heterogeneity, we recommend that an average value be determined from multiple sections when employing this technique.

Hyposplenism from Mycobacterium avium complex infection in a patient with AIDS and immune thrombocytopenia.

We describe a patient with HIV-related immune thrombocytopenic purpura with known Mycobacterium avium complex (MAC) infection presenting with intracerebral hemorrhage associated with severe thrombocytopenia who failed splenectomy following unsuccessful trials of corticosteroids and intravenous immunoglobulin. His presplenectomy peripheral blood smear showed Howell-Jolly bodies and microscopic examination of his spleen demonstrated multiple granulomas with numerous acid-fast organisms replacing the normal splenic tissue. We postulate that splenic hypofunction secondary to overwhelming MAC infection contributed to the failure of the thrombocytopenia to promptly respond to splenectomy.

An Unusual Late Relapse in Pathologic Stage I Non-Seminomatous Germ Cell Tumor: Case Report and Review of the Literature

Late relapses are exceedingly uncommon in patients with pathologic stage (PS) I non-seminomatous germ cell tumors (NSGCT) of the testis treated with inguinal orchiectomy and retroperitoneal lymph node dissection (RPLND). We describe an unusual patient with PSI NSGCT who relapsed 40 months after surgery. The only evidence of recurrent disease was an elevated serum alpha-fetoprotein level, and complete remission was achieved following the prompt institution of combination chemotherapy. To our knowledge, this is the first report of a late relapse in PSI NSGCT of the testis manifested only as an elevated tumor marker.

The clinical oncology career development award of the american cancer society. A 5‐year evaluation

Background. In 1985, the American Cancer Society (ACS) replaced their Junior Faculty Clinical Oncology Program with the 3‐year Clinical Oncology Career Development Award (COCD A). It was proposed that the longer duration and larger stipend of the COCDA would have a greater impact in encouraging promising young clinical oncologists to enter and remain in academic oncology. The COCDA was evaluated at this time to determine whether these goals had been achieved.