Diego Tummarello

Symptomatic, stage IV, non-small-cell lung cancer (NSCLC): response, toxicity, performance status change and symptom relief in patients treated with cisplatin, vinblastine and mitomycin-C

In a series of 46 symptomatic patients with metastatic, stage IV, non-small-cell lung cancer (NSCLC), we used a three-drug combination with cisplatin (120 mg/m2), vinblastine (6 mg/m2) and mitomycin-C (6 mg/m2) (PVM), repeated every 3 weeks. After two courses, we observed that none of the patients had achieved a complete response; 33% (15/46) had partial response (95% confidence limits: 19.2–46.8); 39% (18/46), stable disease and 28% (13/46), progressive disease. Median response duration was 14.0 weeks (range, 4–36.7), median time to progression 22.4 weeks (range, 7–44.4), and median survival time 26.4 weeks (range, 1–103). WHO grade III–IV myelotoxicity occurred in 15.2% of the courses administered, affecting 39.5% of patients, and severe nephrotoxicity was observed in 9.3% of patients. No toxic death occurred. The post-treatment KPS score increased in 7 patients with partial response (47%), 4 with stable disease (22%) and 1 with progressive disease (8%), while it decreased in 3 patients with partial response (20%), 3 with stable disease (17%) and 10 with progressive disease (77%). In all, KPS increased in 12/46 cases (26%). However, no statistically significant difference was observed when the KPS score before and after treatment was compared in the total group of patients or when it was compared in responders and in non-responders. After chemotherapy, there was complete disappearance of at least one symptom in 27.1% of cases and improvement in 27.1%. Overall, major symptom control occurred in 54.3% of cases, with a median palliation time lasting 10 weeks (range, 4–32). Patients with partial remission and stable disease achieved symptomatic palliation in 90% and 55.5% of cases, respectively. When we compared the palliation rate between responders and non-responders, a significant difference was noted (Chi-square test:P<0.05). Although our schedule did not produce a higher objective response rate and the KPS score was not significantly improved, the symptom palliation appeared worthwhile considering the highly unfavourable prognosis of the patients investigated.

Chemotherapy or not in advanced non-small cell lung cancer?

Abstract The value of chemotherapy (CT) in patients with advanced non-small cell lung cancer remains controversial. In the past 10 years results from 7 randomized studies of polychemotherapy vs best supportive care (BSC) have been published: median survival ranges from 8.5 to 21.4 months in BSC arms and from 19.7 to 36.4 months in CT arms. All the studies generally indicate some survival advantage for CT compared to BSC but the difference is statistically significant only for 3 of the 8 regimens tested. Evaluation of effects of treatment on quality of life has been attempted in 2 of the studies, but it has been impossible to obtain results. Indirect parameters (e.g. performance status, etc.) do not show detectable differences between the two groups of patients. The small survival benefit coupled with the low response rate suggests that a major role can be played by patients with stable disease, where the characteristics of the tumor may be more determinant than the choice of the drugs. To date no standard therapy exists for advanced NSCLC and clinical trials on this topic should: (a) include a BSC arm; (b) aim at identifying subgroups of patients who are likely to benefit from CT; (c) analyse in detail toxic side effects; (d) collect information on quality of life and costs of treatment.

Assessing quality of life in patients with cancer: a comparison of a visual-analogue and a categorical model.

A simple instrument for self-assessment of quality of life (QL) in patients with cancer was elaborated using a linear analogue scale (LAS). The instrument was based on five questions, exploring different functional areas; the same questions were also addressed in a parallel format, where problems were seen from an opposite point of view (positive/negative). The LAS was given to 222 patients, for a total of 372 tests collected. Internal consistency was satisfactory (Cronbachs alpha = 0.75); QL score was significantly correlated to parameters of disease. Concordance between scales, as judged by comparison of parallel formats, was statistically significant but poor. A questionnaire was then elaborated with similar items, based on a categorical scale. A direct comparison between LAS and our questionnaire was made on a group of 41 patients. Internal consistency was poor for the LAS (alpha = 0.58) and good for the questionnaire (alpha = 0.93); Spearmans rank correlation coefficients were disappointing for the LAS and good for the questionnaire; the questionnaire was judged reliable in 82.9% of cases, the LAS in 29.3% only; the questionnaire score, and not the LAS score, was significantly correlated with PS and disease status. In conclusion, many patients appeared unable to correctly interpret the visual-analogue scale; the categorical scale was more immediate and correctly understood by the large majority of patients; the correlation between score and important parameters of QL was maintained, and internal consistency was excellent, indicating a satisfactory reliability of this instrument.

Teniposide as Single Drug Therapy for Elderly Patients Affected by Small Cell Lung Cancer

From January 1987 to December 1990, 26/105 previously untreated patients affected by small cell lung cancer (SCLC), not suitable for intensive SCLC treatment since 19 of them were older than 70 years and 7 suffered from severe chronic diseases, received induction therapy consisting of teniposide alone, 60 mg/m2 on days 1-5, every 3 weeks until disease progression. After a minimum of two courses, 24 patients were evaluable for response: 13 with limited disease (LD) and 11 with extensive disease (ED) (2 patients were unevaluable: 1 early death and 1 protocol violation). Response rate, by disease stage, was: in the 13 LD, 1 complete response (CR), 8 partial responses (PR), 2 minor responses and 2 failures; in the 11 ED, 1 CR, 4 PR and 6 failures. The overall response rate was 58% (14/24) (95% confidence limits = 38-78%), comprising 8% CR and 50% PR. Median duration of response was 7 months (range 2-32). Median overall duration of survival was 9 months (range 1.5-36+). Toxicity was haematological WHO grade III in 13% of courses delivered, whereas no further important side-effects were recorded, excluding alopecia, which was common. Teniposide used alone appeared a safe and effective palliative treatment for poor-risk patients; the major limitation was the low CR rate.

Analgesia with epidural calcitonin in cancer patients.

We evaluated the analgesic effect of salmon calcitonin (sCT) on 14 patients with intractable cancer pain. The drug was administered by epidural infusion (4–8 bolus administrations in 48 h); the dosage was 100 IU/48 h in 5 patients and 400 IU/48 h in 9 patients. Significant, although limited, pain relief and nocturnal pain relief were obtained; the requirement for conventional analgesic drugs was substantially reduced. The treatment was well tolerated and no side effect was recorded. However, only in 3/14 patients did pain relief result in improvement of mobility, with two patients becoming able to ambulate; no patient experienced absence of pain. In general, the treatment produced only limited benefit and subsequent morphine treatment was required in all instances. Widespread use of epidural sCT in intractable cancer pain is not justified as a routine procedure and more substantial evidence is required to support the clinical utility of such an approach.

Involvement of the Central Nervous System in Non-Hodgkin's Lymphoma

Fifteen of 146 (10 %) adult patients with non-Hodgkins lymphoma showed clinical and pathologic evidence of involvement of the central nervous system (CNS); in 6 patients, the CNS lymphoma was present at the onset of disease, in 3 of them it was the only sign detected. In the remaining 9 cases, CNS involvement appeared during the course of systemic disease. In all cases symptoms related to infiltration of the CNS were associated with advanced disease (stage IV); bone marrow or bone involvement was found in 9 patients (60 %). The histologic subtypes were mostly of high-grade malignancy according to the Kiel classification: immunoblastic (3), centroblastic (3), Burkitt type (2), lymphoblastic (1), LP immunocytoma in polymorphic variant (3), unclassifiable (3). The prominent signs and symptoms of CNS lymphoma are listed: the cranial nerve palsies are the most common finding. The principal means of detecting CNS involvement are discussed: cerebrospinal fluid cytology, brain scan and CAT scan were the most useful diagnostic procedures. The reported data allow identification of patients at high risk of CNS lymphoma: this includes histologies of high-grade malignancy, advanced stage of disease, and bone marrow or bone infiltration. Therefore, either intensive systemic chemotherapy or CNS prophylaxis are recommended for patients with high risk of CNS disease.

Etoposide and mitomycin-C in pretreated metastatic breast cancer.

Twenty-five patients with metastatic breast cancer in progression after prior chemotheray ± hormonotherapy were treated with etoposide 50 mg/m2 i.v. days 1 to 5 every 21 days and mitomycin-C 10 mg/m2 i.v. day 1 every 42 days. A partial response (PR) occurred in 10 patients with an overall response rate of 40 % (47 % when only the 21 patients evaluable after 3 courses or more were considered). The median duration of PR was 10.5 months (range 3-31). The soft tissue metastatic sites were the most responsive. Toxicity was mild.

Non-small cell lung cancer. Neuroresection of the solitary intracranial metastasis followed by radiochemotherapy.

Fifteen selected patients with advanced intrathoracic non‐small cell lung cancer and solitary metastasis were treated by a combined program including craniotomy, brain and chest irradiation, and systemic chemotherapy. One patient died because of cerebral hemorrhage after the operation. Five patients failed to achieve neurologic benefit. Nine patients improved their neurologic grading, and the median duration of improvement was 10 months (range, 1‐26 months). The responses to systemic treatment were: one complete response, three partial responses, six stable disease responses, and four progressive disease responses. The overall median survival was 6 months from craniotomy and 12 months from diagnosis. Five patients became long survivors; they had a survival time ranging between 12 and 26 months after craniotomy. In conclusion, one third of patients had a satisfactory response to treatment; this outlines the value of the combined aggressive therapeutic approach also performed in patients who had a highly unfavorable prognoses.

Lymphangitic carcinomas of the lung as presentation of prostatic cancer. A case report.

Lymphangitic carcinomatosis of the lung Is a late and often fatal manifestation of cancer. We describe a case of a biopsy-proved pulmonary lymphangitic carcinomatosis in an asymptomatic 61-year-old man. The pulmonary picture proved to be the initial sign of a prostatic cancer. Therapy with LH-RH analogues and antiandrogens achieved a complete clearance of lung involvement.

Phase II trial with alternating two drug schedules, CAP/MEC', for advanced (stage III Mo/M1) non-small-cell lung cancer.

Sixty-eight evaluable patients with advanced squamous cell carcinoma (48), large cell carcinoma (2) and adenocarcinoma (18) of the lung were treated with a six-drug regimen delivering two monthly alternated combinations. The combinations were cisplatin, adriamycin and cyclophosphamide (CAP) and methotrexate, etoposide and CCNU (MEC). Following a minimum of two courses, the overall response rate was 22 % (confidence limits, 12% to 32%) (15/68, 2 complete responses and 13 partial responses); 47 % (32/68) had stable disease and 31 % (21/68) had progressive disease. The responses lasted a median of 3 months (range, 1-15 months). The actuarial median survival was 11 months in responsive patients, 10 months in stable disease patients, and 5 months in progressive patients. The overall median survival obtained was 9 months (range, 2-28+ months). Toxicity was minimal, and subjective tolerance of the treatment appeared good. However, this alternating program did not improve response rate or survival.