Gemcitabine for relapsed or resistant lymphoma.

BACKGROUND: Gemcitabine therapy has not been widely assessed in the treatment of hematological malignancies. We have examined the efficacy and safety of gemcitabine in patients with relapsed or resistant lymphoma. PATIENTS AND METHODS: Gemcitabine (1 g/m2) was given weekly for 7 consecutive weeks, followed by a week off treatment. The drug was then given for 3 consecutive weeks, followed by a week off treatment; this regimen was continued until disease progression or drug intolerance. Fifteen patients have enrolled. Most have been extensively pre-treated for advanced diffuse large-cell or mantle-cell lymphoma. RESULTS: The drug was well tolerated; no patient suffered treatment-related sepsis, hemorrhage or death. Non-hematopoietic toxicity led to discontinuation of gemcitabine therapy in two patients. Dose reductions or delays were required for about two-thirds of treatments. Of 13 evaluable patients, one had a complete response, 3 a partial response, 3 stable disease, and 6 disease progression. After 6 infusions of gemcitabine, a patient with advanced Hodgkin's disease has had a complete remission lasting 21 months. CONCLUSIONS: Gemcitabine has substantial activity and acceptable toxicity in heavily pre-treated patients with advanced lymphoma. Further study is warranted.

Bilateral facial nerve palsy secondary to the administration of high-dose paclitaxel.

Bilateral facial nerve palsy is an uncommon occurrence. We describe a case of bilateral facial nerve palsy secondary to a single cycle of high-dose paclitaxel therapy (825 mg/m2), in a woman with breast cancer. Prior to her high-dose therapy, she had a residual grade 2 peripheral neuropathy following treatment with ten cycles of standard-dose paclitaxel (total dose 3200 mg). The features of the peripheral neuropathy due to standard-dose paclitaxel, which can be both motor and sensory, are well described. Cumulative paclitaxel dose is considered a risk factor for development of the neuropathy. Although facial nerve palsy secondary to paclitaxel is not previously reported, other cranial nerve toxicity has been described. Consistent with reports of the reversibility of paclitaxel-induced peripheral neuropathy, the facial nerve palsies in our patient resolved over 23 months. Ongoing studies of high-dose paclitaxel warrant close attention to its cumulative neurotoxic effects, particularly in patients previously treated with neurotoxic chemotherapy.

Invasive squamous cell carcinoma with sporotrichoid metastasis in a patient with cutaneous T cell lymphoma treated with chronic extracorporeal photopheresis.

An 83-year-old Caucasian man with cutaneous T-cell lymphoma developed an aggressive squamous cell carcinoma of the left forearm, which recurred and metastasized after Mohs micrographic surgery and systemic chemotherapy with cis-platin and 5-fluorouracil. He was treated with extracorporeal photopheresis, radiation therapy, PUVA photochemotherapy, and interferon therapy for cutaneous T-cell lymphoma. Aggressive squamous cell carcinoma can occur in the setting of extracorporeal photopheresis.

Cytosine arabinoside and cisplatin for advanced breast cancer. A phase II study of the Cancer and Leukemia Group B.

Forty-four women with advanced breast cancer participated in a prospective clinical trial to evaluate the efficacy and toxicity of a regimen consisting of cytosine arabinoside and cisplatin. All patients had previously received chemotherapy. Three patients (7%) responded to therapy with response durations of 153, 160, and 441 days. The median time to disease progression and median survival time in all 44 patients were 2.3 and 5 months, respectively. This regimen had significant toxicity, with most patients experiencing severe or life-threatening hematologic, renal, or infectious complications. This regimen cannot be recommended for previously treated patients with advanced breast cancer.

Intratumor administration of beta-interferon in recurrent malignant gliomas. A phase I clinical and laboratory study.

We administered doses of 5 to 180 x 10(6) IU of beta-serine-interferon (IFN-beta ser17) twice weekly to 20 patients with recurrent malignant gliomas in a Phase I study. Interferon was given through an Ommaya reservoir connected by a catheter to the tumor cavity. Side effects of interferon therapy occurred in only one patient and consisted of nausea, vomiting, fever, and chills after each treatment, presumably due to rapid diffusion of interferon into ventricular cerebrospinal fluid (CSF). Problems with the Ommaya reservoir (obstruction in two patients and infection in four patients) led to six patients being terminated from the study, and represent the major difficulty with this form of therapy. Although this was primarily a study of interferon toxicity, of 12 evaluable patients, 3 had stable disease for 148, 192, and 539 days; 9 had progressive disease. In addition, we tested the effect of IFN-beta ser17 on the growth of early passage in vitro cultures of malignant gliomas established from patients. Growth inhibition varied from 0% to more than 50%. In all cultures evaluated, the combination of recombinant gamma-interferon plus IFN-beta ser17 enhanced growth inhibition. Further clinical and laboratory study is necessary to better define the therapeutic efficacy of IFN-beta ser17 and the role of combinations of interferons in the treatment of malignant gliomas.

Non-human primate (baboon) anti-gross cystic disease fluid protein-15 antibody infusion in four women with metastatic breast carcinoma.

Four women with metastatic breast carcinoma and elevated plasma levels of human breast gross cystic disease fluid protein of 15,000 dalton monomer size (GCDFP-15) were treated IV with non-human primate (baboon) anti-GCDFP-15 antibody. Three patients were given a single IV infusion of antibody, while the fourth patient received four sequential IV infusions. Antibody dosage patients, after antibody infusion the plasma level of GCDFP-15 decreased to 0 ng/ml and remained there as long as "free" circulating anti-GCDFP-15 antibody was present. The plasma half-life of the antibody ranged between 1 and 40 h and the duration of detectable free antibody ranged from 6 to 240 h. No toxicity was observed for the dosage range of antibody tested. No anti-baboon antibody response was detected. In the patient who received four sequential infusions of antibody partial regression of subcutaneous metastatic nodules occurred. The other three patients showed no clinically detectable changes from the antibody infusion.

Chemotherapy for advanced pancreatic cancer. A comparison of 5-fluorouracil, adriamycin, and mitomycin (FAM) with 5-fluorouracil, streptozotocin, and mitomycin (FSM).

One hundred ninety-six patients with advanced pancreatic cancer were randomized to receive one of two combination chemotherapy programs: FAM (5-fluorouracil, Adriamycin [doxorubicin], mitomycin) or FSM (5-fluorouracil, streptozotocin, mitomycin). Patient characteristics were comparable in both groups. Overall response rates for those with measurable disease (14% on FAM, 4% on FSM) were not significantly different (P = 0.07). There was no significant difference in overall survival between patients treated with FAM and FSM (median survivals of 26 and 18 weeks, respectively). Survival benefits of FAM were significant only for patients with measurable disease. Toxicity of both regimens was acceptable and comparable, aside from greater renal toxicity and more nausea and vomiting with FSM. The results failed to confirm the 35% to 40% response rates previously reported for FAM and FSM in advanced pancreatic cancer.

Vincristine, adriamycin, and mitomycin (VAM) therapy for previously treated breast cancer. A preliminary report.

Fifteen patients with metastatic breast cancer previously treated with chemotherapy were treated with a regimen consisting of vincristine, Adriamycin, and mitomycin. Eleven patients (73%) responded with three complete and eight partial responses. The median duration of response was eight months. While all four nonresponders died within five months, the median duration of survival of responders was 18 months. Toxicity was significant but tolerable. Thus, this preliminary report suggests that this regimen is active in advanced previously treated breast cancer, providing meaningful remissions with acceptable toxicity.

Kaposi's sarcoma following chemotherapy for testicular cancer in a homosexual man: demonstration of cytomegalovirus RNA in sarcoma cells.

A 35-year-old white Jewish homosexual man who had undergone surgery and chemotherapy for an embryonal carcinoma of the testis subsequently developed Kaposi's sarcoma. The neoplasm involved the skin as well as visceral tissues. Tissue derived from a biopsy specimen of one of the skin lesions was used in the in situ hybridization technique for the detection of genetic material. Cytomegalovirus messenger RNA was identified in the neoplastic Kaposi cells in the skin. The significance of this finding is discussed.

Ocular side effects of cancer chemotherapy.

The ocular side effects of cancer chemotherapeutic drugs are relatively uncommon. Patients with cancer may develop ocular problems due to metastases to the eye or central nervous system, side effects and radiotherapy or chemotherapy, or totally independent eye disorders. We present a review of the reported ocular toxicities of chemotherapeutic agents to assist the oncologist caring for such patients.

Meningeal carcinomatosis in small cell carcinoma of the lung.

Small cell carcinoma of the lung is extremely sensitive to chemotherapy and radiation therapy. We describe the case of a patient who had a complete response to such treatment but relapsed with meningeal carcinomatosis. We propose that prophylactic therapy to the spinal cord as well as the brain should be considered in the treatment of patients with small cell carcinoma of the lung.

Diagnosis of primary breast carcinoma through immunohistochemical detection of antigen related to mouse mammary tumor virus in metastatic lesions: a report of two cases.

Recent investigations have established that approximately half of human breast carcinomas contain an immunohistochemically detectable antigen which is cross-reactive with the 52000-dalton major glycoprotein (gp52) of the mouse mammary tumor virus (MMTV). This antigen can be localized in paraffin-embedded sections of routinely fixed tissues using heterologous antibodies to gp52 or MMTV. This report describes two patients with metastatic carcinoma in axillary lymph nodes without any clinical evidence of a primary lesion in the breast or elsewhere. The localization of the gp52-related antigen in paraffin-embedded sections of both metastatic lesions suggested the presence of primary mammary carcinoma. In both instances, this suggestion was ultimately confirmed by the finding of primary lesions in which the gp52-related antigen was also found.

Prostatic cancer with an unusual presentation: polymyositis and mediastinal adenopathy.

A 67-year-old man with prostate cancer presented with acute polymyositis and vocal cord paralysis as a result of mediastinal lymphadenopathy. His clinical course was unusual, with the development of a malignant pleural effusion, supraclavicular adenopathy, and osteolytic bone lesions. Urologic symptoms developed only pre-terminally, and osteoblastic bone metastases were not documented. This case suggests that prostate cancer need not have a simple natural history.

Chemotherapy before radiotherapy and/or surgery for locally advanced squamous cell carcinomas of the head and neck.

Locally advanced (stage III and IV) squamous cell carcinomas of the head and neck are not well controlled with surgery and/or radiotherapy. Trials of chemotherapy before therapy is given for local disease are currently being conducted in an attempt to improve survival and cure rates. Initial studies are preliminary but suggest (1) possible benefit and (2) no excessive toxic effects after surgery and/or radiotherapy. Head and neck surgeons should be aware of the status of these studies.

Myocardial injury immediately following adriamycin administration.

A patient is described who developed chest pain during adriamycin administration given for the first time for small cell carcinoma of the lung. This was associated with the acute onset of atrial fibrillation with a rapid ventricular response. Although no electrocardiographic changes of myocardial ischemia developed, serum isoenzyme studies suggested that myocardial injury had occurred. The patient recovered but died suddenly three weeks later. Physicians should be aware of possible life-threatening arrhythmias developing during or shortly after adriamycin administration.