Stephen P. Richman

Minority cancer patients and their providers : Pain management attitudes and practice

The goals of the current studies were: 1) to determine the pain treatment needs of socioeconomically disadvantaged African‐American and Hispanic patients with recurrent or metastatic cancer and 2) to assess the attitudes of health care professionals who treat them.

Cancer pain management among underserved minority outpatients: Perceived needs and barriers to optimal control

Minority patients with cancer are at risk for undertreatment of cancer‐related pain. Most studies of patient‐related barriers to pain control have surveyed primarily non‐Hispanic Caucasian patients. The purpose of the current study was to explore barriers to optimal pain management among African‐American and Hispanic patients with cancer through the use of structured patient interviews. Structured interviews allowed the authors to probe for previously unidentified barriers to pain management in these populations.

A phase II study of weekly 24-hour infusion with high-dose fluorouracil with leucovorin in colorectal carcinoma.

Twenty-two patients with advanced colorectal carcinoma were enrolled in this study. Ten patients had received prior chemotherapy that included the combination of fluorouracil (5-FU) and leucovorin (LV). All patients required subcutaneous port insertion and portable external infusion pumps to allow outpatient treatment. 5-FU (2,600 mg/m2) was administered concurrently with LV (500 mg/m2) over 24 hours of continuous infusion. The mean steady-state plasma concentration of 5-FU was 10 mumol/L (range, 7 to 14 mumol/L). The 5-FU dose was based on our previous phase I study, in which maximum-tolerated dose (MTD) of 5-FU was determined to be 2,600 mg/m2 in combination with a fixed dose of LV at 500 mg/m2. The treatment was repeated weekly. Twenty-two patients received a total of 560 courses of treatment. Eleven instances of grade 2-3 toxicity were observed: diarrhea (five), stomatitis (three), hand/foot syndrome (three). The overall objective response was 45% (10 of 22) and among previously untreated patients was 58%. Three of the responders achieved complete response (CR), with lung and liver as the metastatic sites. The median duration of survival for the previously untreated patients was not reached at 22 months, and was 10 months for the previously treated patients. These results suggest that short-term infusional therapy of 5-FU and LV in patients with advanced metastatic colorectal cancer generates acceptable toxicity, with equivalent or superior survivability in previously treated and untreated patients versus alternative methods of administration of the two agents.

Comparative study of pamidronate disodium and etidronate disodium in the treatment of cancer-related hypercalcemia.

PURPOSE This multicenter, double-blind, randomized trial was performed to determine the efficacy and safety of pamidronate disodium (APD) in comparison to etidronate disodium (EHDP) in the treatment of cancer-related hypercalcemia. PATIENTS AND METHODS Sixty-five male and female adult patients with cancer and corrected calcium levels of greater than or equal to 12.0 mg/dL after 24 hours of hydration were randomized to receive either 60 mg APD given as a single 24-hour infusion or 7.5 mg/kg EHDP given as a 2-hour infusion daily for 3 days. RESULTS APD normalized corrected calcium levels in 70% (21 of 30) of patients, whereas EHDP did so in 41% (14 of 34) of patients (P = .026). The mean corrected serum calcium level decreased from 14.6 to 10.5 mg/dL in the APD-treated group and from 13.8 to 11.6 mg/dL in the EHDP-treated group within the first week of treatment. There was no difference in response to APD in patients without versus those with bone metastases (78% v 67%). Both drugs were well tolerated. CONCLUSION This study demonstrated that a single 60-mg infusion of APD is safe and more effective than EHDP given at the dose of 7.5 mg/kg for 3 days in the treatment of cancer-related hypercalcemia.

The natural history of resectable metastatic melanoma (Stage IVA Melanoma)

One‐hundred‐two patients with malignant melanoma who had distant metastases surgically resected and were judged to be clinically free of disease (M. D. Anderson Stage IVA melanoma) were studied. The median survival for all the patients from time of diagnosis of stage IVA disease was 18 months. The site of the resected metastases did not appear to influence survival, being approximately the same for the brain (15 months), lung (16 months), intraabdominal (18 months), and skin and/or lymph nodes (23 months). The site of the resected metastases also did not influence the median disease‐free interval. Patients who had metastases resected from several organs at the same time had a median survival of 15 months, which was similar to that of patients with one resected site. Patients who were rendered Stage IVA on several occasions by surgical excisions had a median survival of 36 months. Thirty‐five patients received surgery only and 67 patients received adjuvant chemotherapy, immunotherapy, or combined chemoimmunotherapy after surgery. For the group treated with surgery only, the median disease‐free interval and survival from diagnosis of stage IVA disease were 6 months and 16 months, respectively, and for the adjuvant group 6 months and 21 months, respectively. Specifically, by the type of adjuvant therapy, the median disease‐free interval and survival from stage IVA for 23 patients receiving Corynebacterium parvum were 6.9 and 19 months; for 39 patients receiving BCG, eight months and 26 months; for 24 patients receiving BCG + DTIC, eight and 17.4 months; and for all 51 DTIC treated patients 6.3 and 17.8 months, respectively. Patients receiving BCG had a median survival superior to the surgery only group (P = 0.02). An increase in survival was seen predominantly in patients who achieved IVA status more than once and received BCG. Patients with recurrent soft‐tissue metastases appeared to benefit most from BCG in prolonging the disease‐free interval. Only 1/10 treated by surgery alone had a disease‐free interval longer than 1 year, compared with 9/16 who received BCG (P = 0.01). Stage IVA melanoma appears to be distinctly different in prognosis from Stage IVB melanoma and should be classified separately. Patients with recurrent soft‐tissue disease may benefit significantly from treatment with BCG.

Pain Education for Underserved Minority Cancer Patients: A Randomized Controlled Trial

PURPOSE Previous studies found that African American and Hispanic cancer patients are at risk for undertreatment of pain. We evaluated the efficacy of a pain education intervention for underserved minority patients. PATIENTS AND METHODS Ninety-seven underserved African American and Hispanic outpatients with cancer-related pain were enrolled onto a randomized clinical trial of pain management education. The patients in the education group received a culture-specific video and booklet on pain management. The control group received a video and booklet on nutrition. A research nurse met with each patient to review the materials. We measured changes in pain intensity and pain-related interference 2 to 10 weeks after the intervention, as well as changes in quality of life, perceived pain control, functional status, analgesics, and physician pain assessments. RESULTS Physicians underestimated baseline pain intensity and provided inadequate analgesics for more than 50% of the sample. Although the ratings for pain intensity and pain interference decreased over time for both groups, there was no statistically significant difference between groups. Pain education did not affect quality of life, perceived pain control, or functional status. African American patients in the education but not the control group reported a significant decrease in pain worst ratings from baseline to first follow-up (P < .01), although this decrease was not maintained at subsequent assessments. CONCLUSION Brief education had limited impact on pain outcomes for underserved minority patients, suggesting that more intensive education for patients and interventions for physicians are needed.

High‐dose cisplatin in patients with advanced malignancies

A study was conducted to determine if cisplatin (CDDP) can be given at higher doses than usual, utilizing aggressive supportive measures. Twelve patients were entered into three dose levels of CDDP: level I, 180 mg/m2 given as a short infusion; level II, 220 mg/m2 also given as a short infusion; level III, 200 mg/m2 divided in five daily doses, each infused over 6 hours. In all cases, CDDP was dissolved and given in 250 ml of a 5% saline solution. For levels I and II, intravenous hydration with 200 to 250 ml/hour D51/2NS with potassium and magnesium supplements, was started 24 hours before therapy and continued for 3 to 4 days after, longer if nausea persisted. Mannitol was given before (25% solution, 50 ml bolus) and after (20% solution, 500 ml over 3 hours) CDDP. At level III hydration with the same intravenous (IV) fluids was begun the day before therapy and continued without interruption at 200 to 250 ml/hour for a minimum of 24 hours after the completion of the 5 days of chemotherapy. Each daily dose of CDDP was preceded by injection of mannitol (25% solution, 50 ml bolus) and accompanied by a 6‐hour infusion of 1000 ml 20% mannitol. Three patients received five CDDP courses at level I; 4 patients, seven courses at level II; and 5 patients, seven courses at level III. Ototoxicity was dose‐limiting in three patients at level II. Transient elevation of serum creatinine was seen following two courses at level I and two courses at level II. The renal impairment was asymptomatic in all cases; dialysis was not needed. At level II, leukocyte nadir counts between 1.0 and 2.0 × 103/mm3 were seen following two courses and between 2.0 and 3.0 × 103/mm3 following three courses. Platelet nadir counts below 50 × 103/mm3 were recorded after four courses and between 50 and 100 × 103/mm3 after one course. Nausea and vomiting occurred frequently, but were tolerable. At level III, myelosuppression was dose‐limiting. Nadir leukocyte counts between 1.0 and 2.0 × 103/mm3 followed four courses and between 2.0 and 3.0 followed one course. Nadir platelet counts below 50 × 103/mm3 were seen after three courses; two patients required prophylactic platelet transfusions. Nadirs between 50 and 100 × 103 platelets/mm3 followed three further courses. Ototoxicity and nephrotoxicity did not occur at level III. Responses were seen in all three dose levels in patients with prostate carcinoma, non‐small cell lung cancer, adenocarcinoma of the esophagus, and malignant fibrous histiocytoma. It was concluded that CDDP at a dose of 200 mg/m2, divided in five daily fractions, is tolerable and can be introduced into Phase II trials.

A phase II trial of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin in the treatment of patients with locally advanced breast carcinoma

Traditionally, primary surgical therapy is considered unsuitable for the treatment of patients with locally advanced breast carcinoma (LABC). Multiple reports have documented the efficacy of primary chemotherapy in this group of patients. The purpose of this study was to investigate the efficacy of a multimodality treatment program in reducing distant and local disease relapses in patients with LABC.

Successful control of systemic aspergillus niger infections in two patients with acute leukemia

The diagnosis and successful control of systemic Aspergillus niger infection in 2 adult patients with acute leukemia is reported. During induction therapy, the first patient developed pulmonary infiltrates, skin lesions and abnormal liver function tests. Aspergillus niger was found on skin and liver biopsy. This patient was successfully treated with Amphotericin B and granulocyte transfusions and he remains in remission. The second patient developed a pneumonitis and adynamic ileus with positive sputum and stool cultures for Aspergillus niger. The infection only responded to Amphotericin B and granulocyte transfusions and the leukemia to cytoreductive chemotherapy. The patient later relapsed and died after a febrile illness. Fungi morphologically consistent with Aspergillus were found in the liver at autopsy. Infection with A. niger is rare even in this patient population; however fungal infections have become an increasing problem. The need for a high index of suspicion, especially when an infection is unresponsive to antibacterial antibiotics, the various diagnostic tools, and the need for aggressive therapy are stressed. Amphotericin B is the chemotherapy of choice but may be insufficient in a severely neutropenic host where the simultaneous use of granulocyte transfusions might be lifesaving.

A phase II trial of tamoxifen, premarin, methotrexate and 5-fluorouracil in metastatic breast cancer

Complete remissions in patients with metastatic breast cancer using endocrine therapy or chemotherapy are infrequent. Breast tumors are known to be heterogeneous with respect to estrogen receptor status, and the low complete remission rate may be related to this biochemical heterogeneity. Based on laboratory experiments using human breast cancer cells in tissue culture, a phase II protocol was designed using tamoxifen, premarin, methotrexate, and 5-fluorouracil. Thus far, twenty-nine (29) patients have been entered into this study and twenty-five (25) are currently evaluable for response. Overall response rate was 72%, and 14 of 25 (56%) attained a complete remission. Toxicity was minimal. Median nadir white blood cell count was 5,800 and median nadir platelet count was 252,000. In summary, this combination chemo-hormonal therapy regimen is effective with a more than 50% complete remission rate and minimal toxicity.