Paul J. Petruska

Multimodality therapy for adenocarcinoma of the esophagus

Few reports exist detailing results of multimodality treatment for adenocarcinoma of the esophagus. We have treated 28 such patients using a preoperative regimen consisting of two courses of cisplatin and 5-fluorouracil with radiation (either 3,000 or 3,600 cGy). There were 25 men and 3 women (mean age, 62.9 years; range, 35 to 86 years), and 16 patients were known to have Barretts esophagus. Dysphagia was present for a mean of 2.7 months, and the average weight loss was 6.5 kg. Tumors ranged from 2 to 10 cm in length (mean, 5.2 +/- 1.8 cm) with American Joint Committee on Cancer clinical stage I in 2 patients, stage II in 19 patients, and stage III in 7. Dysphagia improved in 23 patients (82%), and in 8 (29%) no tumor was detected during radiologic and endoscopic staging after neoadjuvant therapy. Four patients refused operation. Esophagectomy via standard Ivor Lewis approach was accomplished in 20 of 24 patients (87%) undergoing operation. There were no operative deaths, and mean hospital stay was 15.5 +/- 11.6 days. Four patients (17%) were complete responders with no tumor in the resected specimen. Actuarial survival in the 28 patients at 1, 2, and 3 years is 71%, 28%, and 20% respectively. Of the 20 esophagectomy patients, 6 are alive with no evidence of disease at 10, 50, 54, 70, 77, and 84 months. Three of these were complete responders. Only 1 of the 8 patients no undergoing resection is alive at 16 months with no evidence of disease after further radiotherapy and chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized prospective study of vindesine versus doxorubicin and cyclophosphamide in the treatment of epidermoid lung cancer

A randomized prospective study was conducted comparing vindesine (VDS) with doxorubicin and cyclophosphamide (D/C) in the treatment of advanced squamous cell carcinoma of the lung. No patient had a complete response. Seven of 28 (25%) patients had partial response (PR) to VDS while one of 19 (5%) had a PR to D/C (P < 0.08). Adding PR plus minor response (MR), ten of 28 (36%) patients responded to VDS while two of 19 (11%) responded to D/C (P < 0.05). Median survival was improved among patients showing PR and MR over those not responding (P < 0.05). This study concludes, VDS is an active agent in the treatment of squamous cell carcinoma of the lung and should be considered for combination chemotherapy and adjuvant trials. VDS toxicity appears acceptable with six weekly doses of 3 mg/m2. The benefit of a maintenance schedule could not be demonstrated.

Phase II Trial of Topotecan by Continuous Infusion in Patients with Advanced Soft Tissue Sarcomas, a SWOG Study

AbstractPurpose: Based upon the hypothesisthat prolonged exposure to the S-Phasespecific agent topotecan would be moreefficacious in the treatment of soft tissuesarcomas than a conventional 5-day scheduleof the drug, the Southwest Oncology Groupperformed a Phase II trial of topotecanadministered as a continuous infusion inadult patients with advanced soft tissuesarcomas. Methods: Patients who had receivedno prior chemotherapy for advanced diseasewere treated with topotecan at a dose of0.50 mg/m2/day on days 1–21 ofrepeated 28 day cycles. Results: Twenty-two patients wereenrolled on the study, of whom 21 wereeligible. No objective responses wereobserved (95% confidence interval of 0–16%). The mediansurvival was 12 months(95% confidence interval of 5–16months). Conclusions: We conclude thattopotecan, given either according to a5-day or a 21-day schedule, has minimalactivity in the treatment of adult softtissue sarcomas.

Simultaneous Presence of t(2;8)(p12;q24) and t(14;18)(q32;q21) in a B-Cell Lymphoproliferative Disorder with Features Suggestive of an Aggressive Variant of Splenic Marginal-zone Lymphoma

We report a case of an aggressive variant of splenic marginal-zone lymphona (SMZL) with circulating villous lymphocytes. The karyotype of all examined cells had multiple structural and numerical abnormalities, including two lymphoma characteristic translocations, t(2;8)(p12;q24) and t(14;18)(q32;q21). Based on a literature review of cytogenetic aberrations of splenic lymphoma with villous lymphocytes (SLVL) and SMZL, this is apparently the first documentation of these two translocations in a case of SMZL, and could reflect the heterogeneity of the disorder.

Atypical prolymphocytic variant of hairy-cell leukemia: case report and review of the literature.

The prolymphocytic variant of hairy‐cell leukemia (HCL‐V) is relatively rare and differs from typical hairy‐cell leukemia (HCL) both clinically and morphologically. Recognition of HCL‐V is important due to therapeutic impact. We report on a case of HCL‐V, atypical in its degree of marrow fibrosis, LgM/lambda monoclonality, expression of CD24, and the ultrastructural presence of ribosomal lamellar complexes. The patient was treated with splenectomy followed by pentostatin, and he achieved a partial response.

Procarbazine-induced hepatotoxicity: case report and review of the literature.

Procarbazine hydrochloride is an oral alkylating agent primarily used as a component of chemotherapy regimens for Hodgkins lymphoma, as well as in regimens for primary central nervous system lymphoma and high‐grade gliomas. Although the prescribing information for procarbazine lists hepatic dysfunction as a potential adverse reaction, we found only one published report with a probable link between procarbazine and liver injury. We describe a 65–year‐old man who developed liver injury due to procarbazine during salvage chemotherapy for non‐Hodgkins lymphoma. The patient had no preexisting liver disease, his lymphoma was without hepatic involvement, and no liver injury developed after initial chemotherapy with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Due to relapse of his non‐Hodgkins lymphoma, salvage chemotherapy with C‐MOPP‐R (cyclophosphamide, vincristine, procarbazine, prednisone, and rituximab) was administered, and the patient developed fever and amino‐transferase level elevation during the second cycle. After discontinuation of all drug therapy, exclusion of other potential etiologies, and resolution of hepatic injury, the patient was rechallenged with procarbazine and again experienced fever with aminotransferase level elevation. His aminotransferase levels promptly returned to normal after discontinuation of procarbazine, and he experienced no further evidence of liver disease. Use of validated scoring systems of drug‐induced liver injury indicated a definitive association between the patients hepatic injury and procarbazine. Based on our experience with this patient, periodic assessment of hepatic function, as suggested in the package insert, is recommended in patients receiving procarbazine.

Procarbazine for non-Hodgkin's lymphoma

Procarbazine hydrochloride is an oral alkylating agent with activity against lymphoma. It is most commonly used in the treatment of Hodgkins disease. The use of procarbazine-containing chemotherapeutic regimens in non-Hodgkins lymphoma fell out of favor with the advent of CHOP. We report two patients with relapsed and/or refractory follicular lymphoma that achieved a complete and durable remission with a prolonged course of daily procarbazine.

Acute myeloid leukemia induction with cladribine: Outcomes by age and leukemia risk

Acute myeloid leukemia (AML) induction traditionally includes seven days of cytarabine and three days of an anthracycline (7 + 3). Because of evidence of increased efficacy of cladribine combined with this regimen, we conducted a retrospective analysis of 107 AML patients treated with idarubicin, cytarabine and cladribine (IAC) at our institution. Complete remission (CR) occurred in 71%, with overall response of 79%. One-year survival overall was 59%, with 47% (27/57) among patients ≥60 years old and 72% (36/50) in those <60 (Relative Risk [RR] 1.9, 95% CI 1.2-3.2). Median overall survival was 17.3 months in all patients and Cox proportional hazard ratio (HR) for death was 2.2 (95% CI 1.3-3.6) for age ≥60 years compared to <60 years. One year survival was 100% among favorable NCCN risk patients versus 64% in intermediate-risk and 35% in poor-risk patients (p < 0.001). HR for death in intermediate- risk (4.2, 95% CI 1.5-12) and poor-risk (8.4, 95% CI 3.0-24) compared to favorable risk AML was higher than that associated with age ≥60 years (HR 2.2). We conclude that IAC is an effective AML induction regimen, NCCN leukemia risk predicts survival better than age in our population, and high intensity regimens can be justified in selected older patients.

Modified escalated BEACOPP as salvage chemotherapy in classic Hodgkin lymphoma

Current salvage chemotherapy programs for treatment of relapsed or refractory Hodgkin lymphoma are unsatisfactory, with reported complete remission rates not greater than 50% [1]. Escalated BEACOPP chemotherapy provides excellent disease control in upfront treatment of the disease [2, 3]. We are aware of one report describing the use of this regimen in ten patients with relapsed/refractory disease to primary chemotherapy with ABVD, in which a 50% progression-free survival at 3 years was reported [4]. An accompanying editorial by German authors cautions against the use of this regimen in the salvage setting, particularly given the prior exposure to anthracycline with ABVD, and that the standard of care currently is autologous hematopoietic stem cell transplant for the majority of relapsed patients [5]. We report a small series of patients treated at our center with a modified version of escalated BEACOPP substituting doxorubicin with epirubicin, a potentially less cardiotoxic anthracycline. Each patient subsequently underwent an uncomplicated autologous hematopoietic stem cell transplant. We are aware of no other reports utilizing this approach. See Table 1 for patient characteristics and treatment results. 2 Reports