Faculty Bibliography

Anthracyclines and platinums have activity in GYN, lung, breast and upper GI tumors, lymphomas and sarcomas. C and PLD (Doxil, Caelyx) have non-overlapping toxicity profiles: C produces myelosuppression, nausea and peripheral neuropathy while PLD causes schedule-dependent mucocutaneous toxicity. This study aimed to define the RPTD of the two agents in combination. Design: Patients (pt) received C and PLD on D1 of a 21 day schedule. 5 dose levels (DL) were studied (C AUC / PLD mg/m2): DL1: 4/20; DL2: 4/25; DL3: 4/30; DL4: 5/30; DL5: 6/30. DLT were febrile neutropenia, G4 heme or G3 non-heme toxicity other than hypersensitivity (HSR). Pt with heme toxicity could omit C in later cycles and continue PLD until disease progression. Pt with mucocutaneous toxicity extended the PLD dosing interval to 28 days. Results: 20 pt were treated: 7M/13F. Age: med 58.5, range 36-85. Tumors: ovarian (EOC)(7), MMT (2), endometrial (1), cervix (2), H&N (3), NPC (2), leiomyosarc (1), breast (1), islet cell (1). Prior chemo: 13. Pt received a median of 4 cycles of C/PLD (range 1-8) and 8 pt received maintenance PLD after cessation of C. No DLT occurred at any DL. At DL5 (n=6 eval), C1 toxicities were G1-2 ANC/Hb (4), G2 vaginal mucositis (1), G2 HSR (1), G1-2 nausea/vom (2), G2 fatigue (1), G2 hand-foot syndrome (1), G1 diarrhea (1). No cardiac events were observed. RECIST responses were observed in 4 pts (MMT 2, NPC 1, EOC 1). In pt with EOC, Ca125 responses were seen in 4/4 evaluable pt. Conclusions: C and PLD can be safely administered together at full dose, and maintenance PLD is feasible. This combination warrants phase III evaluation in ovarian cancer and may be a useful regimen in other solid tumors. Supported by M01 RR00096 and the Lynne Cohen Foundation for Ovarian Cancer Research

Melanoma, if detected early, is a curable malignancy. Unfortunately, however, many melanomas are detected at the stage that puts patients at a high risk of recurrence, if they are not already metastatic. New techniques are being developed to try to detect subclinical disease and allow for early intervention with adjuvant treatment. Because the incidence of melanoma is on the rise, there is a greater demand to improve the current therapy. Revision of the American Joint Committee on Cancer staging system has enabled patients to be stratified better into risk groups, which in turn dictates treatment recommendations. As evidenced by the data provided, the current chemotherapeutic options for metastatic melanoma are far from optimal. Clearly, in this malignancy, enrollment into a clinical trial is an excellent option for patients. The development of novel approaches to treating this disease provide hope for better management and possible cure of a notoriously aggressive disease with a dismal prognosis

This study investigated the toxicity and efficacy of a 13-cis retinoic acid, carboplatin, and paclitaxel (Taxol) regimen in 18 patients with recurrent or metastatic squamous cell carcinomas (12 head and neck, 4 cervix, 1 esophagus, and 1 anus). Three patients were treated at each dose level with fenretamide (Accutane) 1 mg/kg/d orally for 14 days, carboplatin AUC of 5 mg/ml.min intravenously (IV) and paclitaxel at a dose of 135, 155, 175, 195, 205, or 225 mg/m(2) IV on day 8 every 4 weeks for 6 cycles. Fifteen evaluable patients had a total of 72 treatment cycles. There were 21 grade III or IV toxicities distributed among all the dose levels, including neutropenia, anemia, thrombocytopenia, elevated prothrombin time/partial thromboplastin time, elevated alkaline phosphatase, weight loss, alopecia, and three deaths from aspiration pneumonia and septic shock. The maximum tolerated dosage included 205 mg/m(2) paclitaxel. There was one complete response, three partial responses, and 2 stable diseases. The three partial responses were in the four patients with cervical cancer. Responses did not correlate with expression of retinoic acid receptor subtypes. Toxicity profiles and overall response rates were comparable to prior studies with similar chemotherapy regimens alone. The data support further study in a phase II trial

Immunoproliferative small intestinal disease (IPSID) is a subtype of lymphoma of mucosa-associated lymphoid tissue. Notable for a high production of alpha-heavy chains, it is designated alpha-heavy-chain disease. IPSID is a debilitating disease that has a predilection for impoverished populations of developing countries. It has been documented primarily in subjects of Middle Eastern countries and thus was previously referred to as Mediterranean lymphoma. We report the case of a 42-year-old man from Senegal who presented with chronic diarrhea, dehydration, and weight loss. The endoscopic, pathologic, and serologic findings before, during, and after treatment with fludarabine phosphate are presented. We review the literature concerning current concepts on the etiology, pathogenesis, and management of IPSID

PURPOSE: Low-grade, small lymphocytic lymphomas of the mucosa-associated lymphoid tissue (MALT) have recently been shown to be associated with Helicobacter pylori infections. Regression of these tumors has been reported with antibiotic therapy. Here we evaluate endoscopic ultrasound (EUS) as on objective method to evaluate pretreatment disease and posttherapy response. MATERIALS AND METHODS: We retrospectively reviewed 20 patients initially diagnosed elsewhere with MALT lymphoma. All patients had their initial endoscopic biopsies (EGDs) reviewed at Memorial Sloan-Kettering Cancer Center (MSKCC). All patients had EUS performed at the time of consultation and on completion of therapy if treated at our center. Antral biopsies were stained with a modified Steiner preparation to determine infection by H pylori. RESULTS: Gastric low-grade lymphoma was confirmed in 16 of 20 patients; 11 of 16 had previously received antibiotic therapy for biopsy-positive H pylori infection. All gastric lymphomas had an abnormal EUS: eight with discrete tumor masses and eight with gastric wall infiltration (submucosa, n = 4; muscularis propria, n = 3; serosa, n = 1). On completion of lymphoma treatment with chemotherapy, radiotherapy, or surgery, 11 of 16 patients underwent follow-up EUS. Five patients received care elsewhere and did not return for posttreatment EUS. The gastric wall was normal with no evidence of disease on EUS-guided biopsy in eight of 11 patients. The remaining three patients had abnormal gastric walls. One was biopsy-negative and two had residual lymphoma. Four patients were found to have benign lymphoid aggregates in association with H pylori on initial EGD and EUS biopsies. All four patients were previously untreated with antibiotics. EUS showed prominent mucosa, but no significant findings within the gastric wall. CONCLUSION: EUS appears useful to stage objectively and evaluate therapeutic outcome in the management of gastric, low-grade MALT lymphomas. It also helps to distinguish benign lymphoid aggregates from lymphoma associated with H pylori infection. EUS findings may have a significant impact on assessment and therapeutic recommendations