Charlotte Jacobs

A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck.

PURPOSE To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer, we compared the efficacy and toxicity of cisplatin (CP) and fluorouracil (5-FU), alone and in combination in a phase III trial. PATIENTS AND METHODS Two hundred forty-nine patients with recurrent head and neck cancer were randomized to one of three treatments: CP (100 mg/m2) and 5-FU (1 g/m2 x 4), CP, or 5-FU every 3 weeks. RESULTS The overall response rate to the combination (32%) was superior to that of CP (17%) or 5-FU (13%) (P = .035). Response was associated with good performance status (PS) but not with primary site, site of recurrence, histology, prior irradiation, or relative dose intensity. Median time to progression was less than 2.5 months, and there was no significant difference in median survival (5.7 months) among the groups. By multivariate analysis, patients with better PS and poorly differentiated tumors had superior survival. Hematologic toxicity and alopecia were worse in the combination arm. CONCLUSION Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents, survival did not improve.

Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer: update of a Northern California Oncology Group randomized trial.

Between 1978 and 1984, the Northern California Oncology Group (NCOG) conducted a randomized trial to study the efficacy of combined radiotherapy (RT) and chemotherapy (CT) for stage III or IV inoperable head and neck cancer. One hundred four patients were randomized to receive: (1) RT alone, or (2) RT plus CT. RT consisted of 7,000 cGy to the involved areas and 5,000 cGy to uninvolved neck at 180 cGy/fraction, five fractions/wk. CT consisted of bleomycin, 5 U intravenously (IV), twice weekly during RT, followed by bleomycin, 15 U IV, and methotrexate, 25 mg/m2 IV weekly for 16 weeks after completion of RT. Fifty-one patients in the RT alone group and 45 in the combined treatment group were evaluable. The local-regional complete response (CR) rate was 45% v 67% (P = .056); the 2-year local-regional control rate, including salvage surgery, was 26% v 64% (P = .001); and the incidence of distant metastasis was 24% v 38% (P greater than .25), for the RT alone and RT plus CT groups, respectively. The relapse-free survival curves were significantly different (P = .041), favoring the combined treatment. However, the survival curves were not significantly different (P = .16). Patient compliance to maintenance CT was poor. Bleomycin significantly increased the acute radiation mucositis, although the difference in late normal tissue toxicity was not statistically significant. Thus, bleomycin and concurrent RT produced a more favorable CR rate, local-regional control rate, and relapse-free survival, but the difference in survival was not statistically significant.

Chemotherapy as a Substitute for Surgery in the Treatment of Advanced Resectable Head and Neck Cancer A Report From the Northern California Oncology Group

This trial determines the feasibility for patients with resectable Stages III/IV head and neck cancer who achieved a complete response to induction chemotherapy of eliminating surgery from their treatment program. Thirty patients were treated with three cycles of cisplatin and 5‐fluorouracil (5‐FU), followed by reendoscopy and biopsy. Twelve patients achieved a complete pathologic response at the primary and received radiation (interstitial and/or external beam) only. The remainder underwent surgical resection and postoperative radiation. At 2 years, the relapse‐free survival was 52%, and the survival was 53% for the entire group. For the 12 complete responders who had surgery eliminated, the relapse‐free survival was 60%, and the survival was 70%. This pilot study suggests that for patients with resectable disease who achieve a complete pathologic response to induction chemotherapy at their primary, it is feasible to omit surgery and treat with primary radiation without compromise in survival. This approach warrants further study in a randomized trial.

Behavior of cancer patients: a randomized study of the effects of education and peer support groups.

TWO PROSPECTIVE, CONTROLLED STUDIES were conducted to determine if psychological and social functioning could be enhanced in patients with Hodgkins disease by either education or participation in a peer support therapy group. Eighty-one patients were evaluated with the Cancer Patient Behavior Scale prior to and following intervention. Following education, patients experienced significant improvement in the frequency of Anxiety, Treatment Problems, Depression, and Life Disruption (p ≤0.1) compared to a control group. Following participation in peer support groups, patients showed no improvement in any of 10 areas of life functioning. Thus education represents an effective, efficient, and inexpensive means of improving psychological and social behavior in patients with Hodgkins disease. Participation in this peer support therapy group did not result in significant behavior change.

Efficacy of adjuvant chemotherapy for patients with resectable head and neck cancer: a subset analysis of the Head and Neck Contracts Program.

To evaluate the efficacy of adjuvant chemotherapy for patients with advanced head and neck squamous cancer, the Head and Neck Contracts Program conducted a three-arm study comparing standard surgery and radiation, induction chemotherapy (cisplatin and bleomycin) plus standard therapy, and induction chemotherapy plus standard therapy followed by maintenance cisplatin for 6 months. As previously reported, this trial of 462 patients demonstrated no significant difference in disease-free survival or survival, but a significantly lower metastatic rate in the maintenance arm. To determine whether particular subgroups may have benefited from adjuvant therapy, we evaluated results based on primary site, and tumor (T) and node (N) stage. Of the 192 patients with oral cavity cancer, those on the maintenance arm had a significantly improved 3-year disease-free survival (67%) compared with the standard arm (49%) or induction arm (44%) (overall P = .05). For hypopharyngeal and laryngeal cancers there was no marked overall benefit. For the 106 patients with T1 plus T2 disease, there was marginal improvement in disease-free survival for the maintenance group (72%) compared with the standard group (47%) or induction group (43%) (overall P = .09). There was no advantage for patients with T3 and T4 disease. There was superior disease-free survival for patients with N1 disease on the maintenance arm (70%) compared with the standard arm (42%) (P = .024). The same was true for disease-free survival in 109 patients with N2 disease: standard (52%), induction (30%), maintenance (84%) (overall P less than .001). There was no benefit for N3 disease. A significant survival advantage with maintenance chemotherapy was only seen for N2 disease (overall P = .04). Since head and neck cancer patients are a heterogeneous group, there may be particular sites and stages for which adjuvant chemotherapy would be advantageous, and subset analysis can help indicate directions for new trials.

24-Hour infusion of cis-platinum in head and neck cancers

Eighteen patients with advanced squamous cell cancer of the head and neck were treated with cis‐diamminedichloroplatinum in a 24‐hour infusion. The most frequent dose used was 80 mg/m2 repeated every three weeks. Six were treated preoperatively for Stage III or IV disease, and twelve were treated for recurrent disease. The overall response rate was 72% with one complete remission, >50% regression in six patients, and 25‐50% regression in six patients. Toxicity was minimal: creatinine >2 in 6% of courses, leukopenia in 9%, anemia in 29%, vomiting in 76%, and documented minimal hearing loss in one patient. Plasma and urine platinum levels during infusion are presented. The dosage of 80 mg/m2 administered over 24 hours gives a response rate in head and neck cancers equivalent to that reported with higher doses given by rapid infusion, and toxicity is minimal. Cancer 42:2135–2140, 1978.

Non-Hodgkin's lymphomas of head and neck extranodal sites

The initial staging, therapy and course of 156 patients with non-Hodgkins lymphomas of head and neck extranodal sites were analyzed to determine whether they have a natural history which differs from primary nodal disease. The sites involved were: Waldeyers ring-103 patients (tonsil-60, nasopharynx-25, base of tongue-18), and extralymphatic sites-53 patients (salivary gland-20, paranasal sinus-20, oral cavity-10, and larynx-3). Seventy-six percent had unfavorable histologies and 24% had favorable histologies. Fifty-three percent had pathologic Stages I-II and 47% had Stages III-IV. The 5-year survival was influenced by primary sites: salivary gland-61%, oral cavity-57%, tonsil-49%, base of tongue-47%, nasopharynx-36% and paranasal sinus-12%. The 5-year survival was also influenced by histology: unfavorable histologies-39%, favorable histologies-69%. The Ann Arbor staging system was more useful than TNM for determining outcome. For patients with Stage I-II unfavorable histologies treated with radiation alone, the 5-year survival was: involved field-24%, extended field-42%, total lymphoid irradiation-52%. The majority of patients who failed did so in extranodal sites. Forty-one patients with advanced disease received a variety of chemotherapy regimens as the sole treatment. There was a high percentage of CNS recurrence with paranasal sinus lymphoma, and CNS prophylaxis may be necessary. For head and neck extranodal lymphomas, limited radiation is inadequate, and combined modality programs should be considered.

Management of the pregnant patient with Hodgkin's disease.

Fifteen pregnant women with Hodgkins disease were followed. Five patients had irradiation, 1000 to 3000 rad to the neck, mediastinum, or both, during the second or third trimester with normal outcome of pregnancy. One patient had a spontaneous abortion in the first trimester after radiotherapy of 4400 rad to the breast, an estimated fetal dose of 9 rad. One patient who received chlorambucil throughout pregnancy delivered a normal infant. Six patients had therapeutic abortions; one had early induction of labor. In one patient previously treated for supradiaphragmatic Hodgkins disease, detection of a supradiaphragmatic relapse was delayed because of pregnancy. We recommend abortion for patients who develop Hodgkins disease early in pregnancy or who have received chemotherapy or irradiation during the first trimester. During the latter half of pregnancy, asymptomatic disease may be closely followed but early delivery is recommended. Supradiaphragmatic, symptomatic disease can be treated with modified irradiation. For subdiaphragmatic, symptomatic, or extranodal disease, single-agent chemotherapy may be preferable. Treatment requires individualization to insure that the patient will be cured and the fetus protected.

The Treatment Advice of a Computer-Based Cancer Chemotherapy Protocol Advisor

ONCOCIN is a chemotherapy protocol advisor used experimentally in a university oncology clinic. The program combines formal protocol guidelines with judgments of oncologists who have experience adjusting therapy in complex clinical situations. We compared the chemotherapy administered by clinic physicians with the treatment that would have been recommended by ONCOCIN in 415 visits for 39 patients with lymphoma seen before the programs introduction. In 189 visits the program agreed with the therapy actually administered. In a blinded evaluation, four experts on lymphoma failed to find a significant difference between the treatments selected by physicians and those proposed by ONCOCIN. Further analyses showed that ONCOCIN tended to attenuate drug doses or delay treatment more than the experts recommended, whereas the physicians were less likely to attenuate doses to the extent the experts suggested. Our results show that ONCOCIN provides advice on lymphoma treatment similar to the treatment provided in a university oncology clinic.

The value of medical student research: the experience at Stanford University School of Medicine

At Stanford University School of Medicine, students are encouraged to conduct research, requiring a substantial amount of funding and effort on the part of teaching staff. We questioned one graduating class and all medical teachers to determine the value of the research experience to students, as well as staff satisfaction. Seventy‐three per cent of students and 80% of teaching staff responded. Ninety per cent of students had performed research resulting in at least one published manuscript for 75% and a presentation at a national meeting for 52%. Almost all thought the experience taught them to ask questions, review the literature critically, and analyse data. Three‐quarters responded that the experience motivated them to pursue further research, and 60% indicated that they plan a full‐time academic career. The majority of teaching staff who worked with students found it rewarding and thought the student had had a valuable experience. We conclude that our curriculum provides a positive opportunity for students to develop an investigative approach to medical problems.