Susan P. Hubbard

Bleomycin, adriamycin, cyclophosphamide, vincristine, and prednisone (BACOP) combination chemotherapy in the treatment of advanced diffuse histiocytic lymphoma.

A new combination chemotherapy program for patients with diffuse histiocytic and mixed histiocytic-lymphocytic lymphoma was designed to prevent tumor recurrence during the recovery period of each treatment cycle. A myelosuppressive phase consisting of adriamycin, cyclophosphamide, and vincristine was followed by the nonmyelosuppressive agents bleomycin and prednisone to suppress regrowth of lymphoma while allowing for a return in bone marrow function. Twelve of 25 patients (48%) with advanced, previously untreated, diffuse histiocytic lymphoma achieved a complete remission as determined by restaging 1 month after discontinuation of treatment. The median duration of complete response after completion of therapy is in excess of 1 year (range, 5 to 30 months), and no patient has relapsed. Based on previous experience, it is anticipated that the majority of these patients will achieve an extended disease-free survival for what had previously been regarded as an invariably fatal disease.

Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy.

Abstract Eighty patients with advanced ovarian adenocarcinoma were treated in a prospective, randomized trial comparing a four-drug combination — hexamethylmelamine, cyclophosphamide, methotrexate and 5-fluorouracil — with the oral alkylating agent, melphalan. Treatment with the four-drug combination was associated with a significantly increased overall response rate (75 vs. 54 per cent) (P<0.05), more complete remissions (33 vs. 16 per cent) and longer median survival (29 vs. 17 months) (P<0.02) but more severe toxicity than occurred with melphaIan. Patients with minimal residual disease had a significantly higher overall response rate than patients with extensive residual disease (84 vs. 53 per cent) (P<0.05). Patients with advanced disease who achieved a complete remission documented by peritoneoscopy or laparotomy (or both) have a median survival that will exceed three years. The four-drug regimen is more effective than melphalan in the management of advanced ovarian adenocarcinoma. (N Engl J Med 299:...

Prolonged Disease-Free Survival in Hodgkin's Disease with MOPP Reinduction After First Relapse

Thirty-two patients with Hodgkins disease who relapsed after a first complete remission induced by nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) were retreated with MOPP chemotherapy. Nineteen patients achieved a second complete remission. Median duration of the second complete remission was 21 months. The likelihood of achieving a second complete response could be predicted by the duration of the first response. Fourteen of 15 patients whose first complete remission was longer than 12 months achieved a second complete response in contrast to five of 17 patients whose initial complete remission lasted less than 12 months (P less than 0.001). Median survival of all patients in this study who were re-treated with MOPP was longer than 4 years after their first relapse. We conclude that patients with Hodgkins disease who relapse after a first complete remission induced by MOPP are not necessarily resistant to further MOPP therapy and can achieve long-term survival with MOPP reinduction.

Sequential nonsurgical and surgical staging of non-Hodgkin's lymphoma.

The yield of specific diagnostic procedures in the staging of non-Hodgkins lymphoma was assessed in 170 consecutive patients who were evaluated with a sequence of diagnostic procedures. Stage III or Stage IV disease was established in 141 of 170 patients (80%) by nonsurgical procedures, including lymphangiography (positive in 78%), bone-marrow biopsy (positive in 39%), percutaneous liver biopsy (positive in 21%), and peritoneoscopy-directed liver biopsy (positive in 29% of those tested). Staging laparotomy showed disease outside conventional nodal irradiation fields in 21 of 26 patients with a positive lymphangiogram, but in only three of 17 patients with a negative lymphangiogram. The yield of staging procedures was highest in patients with nodular lymphomas, only 6% of whom were Stage I or Stage II after staging, but was lowest in patients with histiocytic lymphoma, 30% of whom had localized disease. This study shows that the presence of disseminated disease can be detected in the majority of patients with non-Hodgkins lymphoma without the use of staging laparotomy.

The chemotherapy of ovarian carcinoma

Ovarian carcinoma is the fifth most frequent cause of death from cancer among women and approximately 14,000 new cases are diagnosed each year of which 10,400 will eventually be fatal (46). Although the mortali ty rate has leveled off somewhat in the past decade, the death rate from this disease has tripled in the past 40 years and more than 1 out of every 100 women in the United States will eventually die of ovarian carcinoma. Although surgery and radiotherapy play major roles in the management of many patients with this illness, approximately 60% of patients initially present with advanced disease (F IGO stages I I I and IV) outside the confines of the truepelvis. Evenafter resection of what appears to be localized disease, 20-50 ~o of women will develop recurrent disease requiring further therapy (2, 40). Thus, for most patients with ovarian carcinoma, some kind of systemic therapy will be required either for pr imary or adjuvant management of advanced disease or for subsequent management of recurrent disease. As a consequence, considerable interest in the use of chemotherapy in this illness has developed over the past decade. This review represents an at tempt to collect the available information on the use of single agents and combination chemotherapy in ovarian carcinoma, and to highlight additional chemotherapeutic agents of potential interest. Finally, a series of studies is proposed which may serve to optimize existing therapy in ovarian carcinoma and provide the basic information required to initiate combined modality studies in a systematic way, comparing newer modalities to optimal existing therapy within each stage.

Chemotherapy of advanced ovarian carcinoma: A prospective randomized comparison of phenylalanine mustard and high dose cyclophosphamide

Twenty-four fully staged, previously untreated patients with advanced ovarian carcinoma were prospectively randomized to either intensive intravenous cyclophosphamide or conventional oral Melphalan therapy. The median durations of initial remissions (5 and 6 mo) and the median durations of survival (15 and 14 mo) were similar for the two regimens but the toxicity of the intensive regimen was excessive. Followup indicates that long term disease free survivals are possible in those patients who achieve complete remissions on chemotherapy alone as three of the four patients achieving complete remission in the present study remain free of disease with a median survival in excess of 30 mo. High dose intensive alkylating agent therapy in the manner used in the present study fails to enhance the response to chemotherapy and produces unacceptable toxicity.

Ocular irritation from high-dose methotrexate therapy: Pharmacokinetics of drug in the tear film

Four of 13 patients receiving intermittent high‐dose methotrexate therapy experienced recurrent symptoms of ocular irritation (burning, pruritus, “dry eyes”) two to seven days after chemotherapy. Ophthalmic examination was unremarkable in symptomatic individuals except for decreased reflex production of tears in some patients. Pharmacokinetic studies of a group of these patients revealed concentrations of methotrexate in tears equivalent to those in plasma at 24 and 48 hours after treatment; these concentrations reached 1 × 10−5 M during the infusion of methotrexate. The occurrence of acidic lacrimal secretions, pH 6.5 in one symptomatic patient, may have contributed to decreased solubility of methotrexate in the fluid of the conjunctival sac.

History of clinical trials

Advances in medical treatments have occurred because of the application of new knowledge gained from clinical experiments conducted over the last 250 years. New sources of compounds with anti-tumor activity in human cancer are constantly under investigation. The development of a new drug is a complex process: screening, formulation, production, toxicology studies, FDA approval, and evaluation in phase I, II, and III clinical trials.

Sequential nonsurgical and surgical staging of non-Hodgkin's lymphoma

The results of clinical and surgical staging in a series of 170 patients with non‐Hodgkins lymphoma are reviewed. Advanced disease (Stage IV) was established without laparotomy in 95 patients (56%), primarily through bone marrow biopsy, closed liver biopsy, and peritoneoscopy. Laparotomy revealed a high incidence of liver involvement and involvement of lymph nodes outside of conventional abdominal irradiation portals only in patients with nodular types of pathology and in patients with positive lymphangiograms. The limitations and indications for staging laparotomy are discussed in the context of these findings.

High dose intravenous bleomycin in the treatment of advanced lymphomas

Abstract Aggressive therapy with high dose intermittent courses of bleomycin ( 25 mg/M 2 daily for five consecutive days) was evaluated in patients with advanced rapidly progressive lymphomas in an attempt to exploit the relative marrow-sparing effects of this drug in patients and to maximize responses early in treatment by reaching a high total dose level over a short time interval. Toxicity was similar to that observed in patients given the lower conventional doses in other studies, but, as could be expected, occurred earlier and at total doses averaging 125–150 mg/M 2 . In spite of the rapid administration of a full therapeutic dose, the response rate in this small group of patients did not seem to be enhanced.