Glenn Cummings

Cisplatin and 5-fluorouracil infusion in patients with recurrent and disseminated epidermoid cancer of the head and neck.

The combination of cisplatin and 96‐hour infusion of 5‐fluorouracil (5‐FU) was evaluated in 30 patients with recurrent (local and regional) and disseminated histologically proven epidermoid cancer of the head and neck who failed surgery and radiotherapy. Cisplatin 100 mg/M2 intravenous (IV) bolus was given on day 1 with hydration and mannitol diuresis; 5‐FU 1000 mg/M2 per day for 96‐hour infusion was started immediately after cisplatin on day 1. All patients had measurable lesions. Eight (27%) patients achieved complete response (CR), and 13 (43%) had partial response (PR). Overall response rate was 70% (8 of 30 CR and 13 of 30 PR). Response rate in patients with recurrent local and regional disease was 89% (17/19) with median survival of 32 weeks, while response in patients with disseminated disease was 36% (4/11) with median survival of 24 weeks. Patients with good performance status (PS) (<70%) had a response rate of 79% (19/24), while those with poor PS (<70%) had a response rate of 33% (2/6). Seven patients with recurrent disease who had a response to this chemotherapy went to further salvage surgical procedures. It is concluded that the combination of cisplatin and 5‐FU is very effective and well tolerated in these patients, and leads to further salvage in some patients with improved longevity and quality of life.

Correlation between response to cisplatinum‐combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck

Induction chemotherapy, followed by surgery and/or radiotherapy was utilized in patients with advanced squamous cell carcinoma of the head and neck. During these trials, the authors observed that response to chemotherapy predicts further response to subsequent radiotherapy. This study was comprised of 57 patients with 60 separate neoplasms who demonstrated less than complete response (partial or no response) to initial treatment with a combination chemotherapy containing cisplatin. Subsequently radiotherapy, either 5000 rad preoperatively or 6600 rad as definitive therapy, was employed. Forty‐one of the 42 tumors with initial partial response to chemotherapy also responded to radiotherapy (97.6%). Only one of the 18 tumors that initially failed to respond to chemotherapy subsequently responded to radiotherapy (5.5%). This observation suggests that patients with head and neck cancer sensitive to initial chemotherapy share parameters that are also radiation sensitive.

Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate.

PURPOSE Estramustine and etoposide (VP-16) have been demonstrated to inhibit the growth of prostate cancer cells in experimental models. This led us to evaluate the effectiveness of this combination in the treatment of patients with metastatic prostate carcinoma refractory to hormone therapy. PATIENTS AND METHODS Estramustine 15 mg/kg/d and VP-16 50 mg/m2/d, were administered orally in divided doses for 21 days. Patients were then taken off therapy for 7 days and the cycle then repeated. Therapy continued until evidence of disease progression. RESULTS Forty-two patients have been enrolled onto this trial with a minimum of 40 weeks follow-up. Of 18 patients with measurable soft tissue disease, three demonstrated a complete response (CR) and six a partial response (PR) for longer than 2 months. Of these 18 patients, pretreatment prostate-specific antigen (PSA) levels decreased by at least 75% in five men (28%) and by at least 50% in nine (50%). The median survival duration has not been reached in those patients who demonstrated a response either by soft tissue or PSA criteria. Of 24 patients with disease limited to bone, six (25%) demonstrated improvement and nine (38%) demonstrated stability in their bone scans. Five men (21%) demonstrated a decrease of at least 75% in pretreatment PSA levels and 14 (58%) demonstrated at least a 50% decrease; the median survival duration has not been reached in these patients. Pretreatment performance status is an important predictor of survival. CONCLUSION We conclude that the combination of estramustine and VP-16 is an active oral regimen in hormone-refractory prostate cancer.

Dose-response and dose-survival advantage for high versus low-dose cisplatin combined with vinblastine and bleomycin in disseminated testicular cancer a southwest oncology group study

One‐hundred fourteen patients with advanced testicular cancer were randomized to treatment consisting of either high‐dose (120 mg/m2, monthly) or low‐dose (15 mg/m2, daily X 5 monthly) cisplatin, both combined with vinblastine and bleomycin. There were 60 (53%) complete remissions and 42 partial remissions for an overall response rate of 90%. An additional 11 patients, 4 with carcinoma and 7 with mature teratoma, following surgical cytoreduction, were rendered free of disease. There was a significantly higher complete response rate for high dose induction chemotherapy, 63%, when compared with low dose, 43% (P = 0.03). A survival advantage was also observed for patients receiving high‐dose therapy (P = 0.009). For the subgroup of patients with maximal disease and embryonal ± teratoma ± seminoma histology there was a clear advantage in favor of high‐dose over low‐dose therapy both in complete response rate and survival (P = 0.03). There have been only four relapses, all occurring within 1 year of study entry. While there has been a higher frequency of leukopenia, renal, neuromuscular, and mucosal toxicity with high‐dose therapy, thus far no irreversable toxicity leading to functional impairment has been seen. The authors have demonstrated a clear‐cut relationship for dose of therapy, not only with response and survival, but with the increased potential for cure as well. Cancer 53:1029‐1035, 1984.

A randomized trial of cisplatin (CACP) + 5-fluorouracil (5-FU) infusion and CACP + 5-FU bolus for recurrent and advanced squamous cell carcinoma of the head and neck

One of the most active chemotherapeutic regimens for treatment of advanced and recurrent head and neck cancer is cisplatin (CACP) + 5‐fluorouracil (5‐FU) infusion with a response rate of 90% in advanced, previously untreated patients and 70% in patients with recurrent disease. Forty‐four patients from two Wayne State University‐affiliated hospitals were entered into a randomized trial of CACP (100 mg/m2) day 1 and 24‐hour infusion of 5‐FU (1000 mg/m2) days 1 through 4 versus CACP (100 mg/m2) day 1 and bolus 5‐FU (600 mg/m2) day 1 and day 8. Thirty‐eight patients were evaluable for three induction courses. Response for the infusion arm was 72% (4/18 complete response [CR] + 9/18 partial response [PR]). Response for the bolus arm was 20% (2/20 CR + 2/20 PR). The difference in response was statistically significant by chi‐square analysis (P < 0.01). Seventy percent of the patients on the bolus arm experienced leukopenia with several episodes of grades 3 and 4 leukopenia. In addition, 50% of the patients on the bolus arm experienced thrombocytopenia. Stomatitis was more frequent on the infusion arm but it was mild and reversible. The complete responders on either arm have a median survival of 120+ weeks; partial responders, 30 weeks. Cisplatin + 5‐FU infusion produces a superior response as initial chemotherapy for three courses compared with CACP and 5‐FU bolus.

Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy

An analysis of preoperative multimodality adjuvant therapy with 5-fluorouracil, mitomycin-C, and radiation therapy revealed that 38 of 45 patients (84 percent) treated were rendered free of cancer after chemotherapy/radiation therapy. No recurrence of tumor has been noted in those patients rendered free of disease by the preoperative treatment. Seven patients (15 percent) with residual macroscopic or microscopic cancer after preoperative therapy have had recurrence, all in distant sites. These seven patients have died from the disease. The prognosis for patients in this series depended on the success of the preoperative therapy in eradicating all tumor prior to surgery. Mitomycin-C and 5-fluorouracil are cytotoxic for local disease and for microscopic distant disease as well. Abdomino-perineal resection is unnecessary for patients whose primary tumor is eradicated by the preoperative therapy. The role of the relatively low dose of radiation therapy needs to be further defined.

Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination in patients with locally advanced head and neck cancer.

In a series of three consecutive pilot studies conducted between 1977 and 1982 at Wayne State University, Detroit, Michigan, 191 consecutive patients with previously untreated, locally advanced head and neck cancer were treated with cisplatin (CDDP), vincristine, and bleomycin or CDDP and 5‐fluorouracil (5‐FU) infusion before definite surgery or radiation. A 39% (75/191) rate of complete clinical responses was achieved. Thirty‐two of the chemotherapy‐induced complete responders underwent radical surgery. Thirteen had no histologic evidence of residual disease in the surgically resected specimen. The CDDP and 5‐FU infusion combination achieved the highest histologic complete response rate. All histologically complete responders who had completed local radiation therapy are clinically free of disease at median follow‐up of 36 months. Patients who achieved complete response both clinically and histologically had superior survival as compared to patients who achieved complete response clinically and were subsequently found to have residual tumor in their surgically resected specimen (P = 0.01). An analysis of the clinical and pathological pretreatment characteristics was performed to identify factors predictive of histologic complete response. Advanced nodal disease correlated inversely with the achievement of negative histology in the surgically resected specimen (P = 0.02). No other factors were significant in predicting response. Cancer 59:233–238, 1987.

Brain metastases in patients with renal cell carcinoma: prognosis and treatment.

Thirty-four patients with renal cell carcinoma and brain metastases were reviewed to define important prognostic factors and treatment results. The following covariates were analyzed to determine their influence on survival: disease-free interval, serum calcium, number of central nervous system (CNS) metastases, weight loss, performance score, age, radiation therapy, surgery, and surgery plus radiation. The mean survival for all patients was 7.0 months (range, seven days to 32 months). The patients with a good performance score of 0-2 survived significantly longer (mean survival, 10.2 months) than those with a poor performance score of 3-4 (mean survival, 2.8 months; p = 0.0019). Surgery was associated with significantly improved survival (mean survival, 13.8 months versus mean survival, 4.2 months; p = 0.014). However, all the surgical patients were from the good performance score group, suggesting patient selection. Radiation was associated with an improved mean survival of 8.6 months versus 3.2 months. Performance score is a significant prognostic factor. Furthermore, the data support treatment with radiation therapy for patients with multiple CNS metastases and surgery followed by postoperative radiation therapy for patients with single CNS metastases.

The Incidence and significance of thromboembolic complications in patients with high-grade gliomas

Coagulation system abnormalities in patients with malignancy ranges from asymptomatic laboratory abnormalities to overt clinical manifestations. To determine the incidence and significance of clinically manifest thromboembolic phenomena in patients with high‐grade gliomas, the records were analyzed of 77 patients that presented between January 1985 and June 1988. Fifteen patients (19%) had clinically manifest deep venous thrombosis and/or pulmonary emboli during the course of their disease. All these patients were ambulatory before and at the time of diagnosis of the event. The thromboembolic episodes occurred at the time of initial management of the primary tumor while there was documented clinical improvement in the functional status of the patient or at the time of progression of the disease. One patient died as a result of a pulmonary embolism; in two others, an embolism was a significant contributor to the patients death. Anticoagulation resulted in complications in two of eight patients treated. Thromboembolic events occur with high frequency in patients with high‐grade gliomas and contribute to the high morbidity and mortality seen in these patients. The optimum approach to screening and the treatment of these events has not been determined. Cancer 68:2621–2624, 1991.

Vesicourethral anastomosis biopsy after radical prostatectomy: predictive value of prostate-specific antigen and pathologic stage.

OBJECTIVES To assess the role of clinical parameters and pathologic stage in predicting a positive vesicourethral anastomosis (VUA) biopsy in patients with a rising prostate-specific antigen (PSA) level after radical prostatectomy. METHODS Forty-five patients were referred for a rising PSA level after radical prostatectomy. Transrectal ultrasound evaluation included visualization of the VUA and VUA quadrant biopsies. The rate of positive biopsies (per core and per patient) was correlated with race, PSA level, and the radical prostatectomy pathologic stage. RESULTS Overall, 53% of patients had a positive biopsy. In multivariate analysis, the dominant independent and synergistic clinical parameters determining positive biopsy rates were a PSA greater than 1 ng/mL at the time of biopsy and the pathologic stage (P = 0.04 and P = 0.02, respectively). Using a PSA cutoff point of 1.0 ng/mL, those patients with organ-confined disease and a PSA of 1.0 ng/mL or less showed no positive cancer cores (low-risk group). Conversely, 89% of patients with extraprostatic extension and a PSA greater than 1.0 ng/mL had a positive biopsy (P <0.01) (high-risk group). Patients with organ-confined disease and a PSA greater than 1.0 ng/mL or extraprostatic extension and a PSA 1.0 ng/mL or less (intermediate-risk group) had a significantly higher chance of having residual cancer than the low-risk group (P <0.025). CONCLUSIONS The PSA level at the time of biopsy and the pathologic stage of the radical prostatectomy specimen were the strongest determinants of a positive biopsy. A combination of PSA and pathologic stage is useful for decisions regarding VUA biopsy. Patients with organ-confined disease and a PSA of 1.0 ng/mL or less do not appear to benefit from a VUA biopsy, and patients with extraprostatic extension and a PSA greater than 1.0 ng/mL have such a high probability (89%) of local recurrence at the VUA that biopsy may be unnecessary. It appears that VUA biopsy can be restricted to those patients with an intermediate risk (organ-confined disease with PSA greater than 1 ng/mL or extraprostatic extension with a PSA less than 1 ng/mL).